Abstract The first-line medications used in clinics for colorectal cancer (CRC) are 5-fluorouracil (5-FU)-based chemotherapy and its prodrug, capecitabine. Nevertheless, there are still relatively few patients responding to 5-FU/capecitabine-based therapy. Up to 30% of patients treated with 5-FU experience early-onset severe toxicity, including diarrhea, nausea, mucositis, stomatitis, myelosuppression, neurotoxicity, and hand–foot syndrome. The catabolism of 5-FU plays a major role in determining its toxicity. Dihydropyrimidine dehydrogenase (DPD) enzyme present in the liver and is encoded by DPYD gene, which inactivates most fluoropyrimidine (FP) molecules, patients with a deficit in DPD are more likely to have significant treatment-related toxicity while using FP on a regular basis. In the present case report, we have documented the case of a 49-year-old female diagnosed with metastatic CRC Stage 4 and evaluated the toxicity produced by the entire dose regimen. The patient had shown Grade IV toxicity from the first dose (5-FU) and continued until shifting to capecitabine and finally adjusting to the S Trio. Despite the high level of toxicity, the patient was found to be negative for the four most common mutant variants of the DPYD gene (c.1905 + 1G>A [*2A], c.1129-5923C>G [HapB3], c.1679T>G [*13], and c.2846A>T). However, the c.2194 G/A variant, which is a normal metabolizer, was found to be positive. Therefore, we document and recommend further studies on variant c.2194 G/A to consider its clinical impact for protective testing, particularly in the Indian population.

Groundwater arsenic poisoning has posed serious health hazards in the exposed population. The objective of the study is to evaluate the arsenic ingestion from breastmilk among pediatric population in Bihar. In the present study, the total women selected were n = 513. Out of which n = 378 women after consent provided their breastmilk for the study, n = 58 subjects were non-lactating but had some type of disease in them and n = 77 subjects denied for the breastmilk sample. Hence, they were selected for the women health study. In addition, urine samples from n = 184 infants’ urine were collected for human arsenic exposure study. The study reveals that the arsenic content in the exposed women (in 55

Arsenic contamination is a serious issue throughout the world and is substantial risk factor in most of the countries including India. Chronic arsenic exposure from drinking water to humans is causing major public health related issues. The present study aims to investigate the ameliorative effect of Citrullus lanatus (Watermelon) seeds against arsenic induced reproductive function and testicular toxicity in Charles Foster rats. In the present study, twenty-four male Charles Foster rats (120±5gm). The study group includes group - I (n=6) as control, and group - II (n=18) treated with sodium arsenite (8 mg per Kg body weight per day) for 90 days. The group - II was furthermore divided into three sub-groups, Group – II-a, Group – II-b and Group – II-c. The group – II-a were sacrificed to see the effect of arsenic toxicity effect after arsenic exposure. Group – II-b was left with normal food and water for next 60 days to observe auto recovery. The group – II-c rats were administered with Citrullus lanatus (Watermelon) hydroxyl ethanolic seeds extract at the dose of 400 mg per Kg body weight per day for 60 days for 90 days upon pre-treated sodium arsenite treated group (8 mg per kg body weight). After completion of the experiment, all the treated group of animals were sacrificed for biochemical, hormonal assay, histopathological, testicular and reproductive functions study. In the arsenic treated rats' group, there was significant (p<0.001) changes in serum levels of SGPT, SGOT, urea, uric acid and creatinine as well as in haematological parameters. There was decrease in the sperm counts and sperm motility accompanied by an increased incidence of sperm abnormalities and hormonal imbalance denotes infertility condition. In contrast, after the administration with C.lanatus (Watermelon) seeds hydroxy-ethanolic extract upon arsenic treated rats group, there was significant (p<0.001) improvement observed in the reproductive, hepatic and renal parameters. In the arsenic intoxicant rats' group, after administration with C. lanatus (Watermelon) seeds hydroxyl ethanolic extract, there was significant (p<001) reduction in the arsenic concentration in blood, liver, and kidney tissues as well as serum lipid peroxidation. The histopathological study also showed the C. lanatus (Watermelon) seeds hydroxy ethanolic extract significantly restored the cellular integrity of testicular cells leading to normal functioning of it against arsenic induced toxicity.

Arsenic poisoning in groundwater is the most common environmental pollutant, which is leading to serious pollution worldwide. Chronic arsenic exposure from drinking water to humans causes major public health-related issues. The present study was conducted to investigate the antidote effects of Foeniculum vulgare (Fennel) against arsenic-induced hepatotoxicity and testicular toxicity in Charles Foster rats. In the present study, twenty-four male Charles Foster rats (120±5gm) were divided into four Groups (n=6), where control Group-I received a normal diet and water; Group - II and Group - III received sodium arsenite (8 mg per kg body weight per day) for 90 days. Group III was left with a normal diet and water for the next 60 days for auto-recovery. The group IV rats were administered Foeniculum vulgare (Funnel) hydroxyl ethanolic seed extract at a dose of 150 mg per kg body weight for 60 days in a 90-day pre-treated sodium arsenite group (8 mg per kg body weight). After complete dose duration, all the treated animals were sacrificed the same day for haematological, biochemical, hormonal, and histopathological studies. In the arsenic treated rats, there were significant (p<0.001) changes in serum levels of SGPT, SGOT, urea, uric acid and creatinine as well as in haematological parameters. And there was also decease in the sperm count and sperm motility, accompanied by an increased incidence of sperm abnormalities and hormonal imbalances leading to infertility. In contrast, after the administration of F. vulgare seeds hydroxy-ethanolic extract to arsenic-treated rats, significant (p<0.001) improvements were observed in hepatic and renal parameters as well as haematological parameters. In the arsenic-intoxicant rat, after administration of F. vulgare seeds hydroxyl ethanolic extract, there was a significant (p<001) reduction in the arsenic concentration in blood, liver, and kidney tissues as well as serum LPO. The histopathological study also showed the F. vulgare seeds hydroxy-ethanolic extract significantly restored the cellular integrity of testicular cells, leading to their normal functioning against arsenic-induced toxicity.

The present study was carried out in the village Kaliprasad of Bhagalpur district of Bihar to know the arsenic exposure effect in the exposed population. A total of n = 102 households were studied, and their water and biological samples such as urine and hair were collected and analyzed in a graphite furnace atomic absorption spectrophotometer (GF-AAS). The assessment of arsenic-exposed village population reveals that the villagers were suffering from serious health-related problems such as skin manifestations (hyperkeratosis and melanosis in their palm and soles), breathlessness, general body weakness, mental disorders, diabetes, hypertension (raised blood pressure), hormonal imbalance, neurological disorders, and few cancer cases. About 77% of household hand pump water had arsenic level more than the WHO recommended level of 10 mu g/L, with highest level of 523 mu g/L. Moreover, in 60% individual's urine samples, arsenic concentration was very high with maximum 374 mu g/L while in hair 64% individuals had arsenic concentration above the permissible limit with maximum arsenic concentration of 11,398 mu g/kg. The hazard quotient (HQ) was also calculated to know the arsenic risk percentage in children as 87.11%, in females as 83.15%, and in males as 82.27% by groundwater. This has surpassed the threshold value of 1x10-6\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$1\times {10}<^>{-6}$$\end{document} for carcinogenic risk (CR) in children, female, and male population group in the village. Hence, the exposed population of Kaliprasad village are at very high risk of the disease burden.

In recent times Gallbladder cancer (GBC) incidences increased many folds in India and are being reported from arsenic hotspots identified in Bihar. The study aims to establish association between arsenic exposure and gallbladder carcinogenesis. In the present study, n = 200 were control volunteers and n = 152 confirmed gallbladder cancer cases. The studied GBC patient's biological samples-gallbladder tissue, gallbladder stone, bile, blood and hair samples were collected for arsenic estimation. Moreover, n = 512 gallbladder cancer patients blood samples were also evaluated for the presence of arsenic to understand exposure level in the population. A significantly high arsenic concentration (p < 0.05) was detected in the blood samples with maximum concentration 389 µg/L in GBC cases in comparison to control. Similarly, in the gallbladder cancer patients, there was significantly high arsenic concentration observed in gallbladder tissue with highest concentration of 2166 µg/kg, in gallbladder stones 635 µg/kg, in bile samples 483 µg/L and in hair samples 6980 µg/kg respectively. Moreover, the n = 512 gallbladder cancer patient's blood samples study revealed very significant arsenic concentration in the population of Bihar with maximum arsenic concentration as 746 µg/L. The raised arsenic concentration in the gallbladder cancer patients' biological samples-gallbladder tissue, gallbladder stone, bile, blood, and hair samples was significantly very high in the arsenic exposed area. The study denotes that the gallbladder disease burden is very high in the arsenic exposed area of Bihar. The findings do provide a strong link between arsenic contamination and increased gallbladder carcinogenesis.

Abstract BackgroundIn recent times Gallbladder cancer (GBC) incidences increased many folds in India. Majority of GBC cases are being reported from arsenic hotspots identified in Bihar. MethodsIn this prospective study volunteers were selected who underwent surgery in our cancer institute. There were 11 control benign gallbladder cases and 28 confirmed gallbladder cancer cases. Their biological samples such as blood, gallbladder tissue, gallbladder stone, bile and hair samples were collected for arsenic estimation. Moreover, n=512 gallbladder cancer patients blood samples were evaluated for the presence of arsenic to understand exposure level in the population. ResultsA significantly high arsenic concentration (p<0.05) was detected in the blood samples, gallbladder tissue, gallstones, bile and hair samples in comparison to the control group. Moreover, n=512 blood samples of GBC patients had significantly very high arsenic concentration. ConclusionsThe study shows very high arsenic concentration observed in the blood, gallbladder tissue, gallbladder stone, bile and hair samples in GBC cases in comparison to the benign control cases indicates the correlation between chronic arsenic exposure and gallbladder cancer incidences in eastern Indo-Gangetic plains region. The study also makes an attempt to establish the likely correlation/association between arsenic exposure and gallbladder cancer disease.

Fast growing arsenic menace is causing serious health hazards in Bihar, India, with an estimated 10 million people at risk. The exposed population is often unaware of the problem, which only amplifies the burden of arsenic health effects. In the present study, we have assessed the current situation of arsenic exposure in Chapar village of Samastipur district, Bihar. The health of the inhabitants was assessed and correlated with (1) arsenic concentrations in the groundwater of individual wells and (2) arsenic concentration found in their hair and urine. Altogether, 113 inhabitants were assessed, and 113 hair, urine and groundwater samples were collected. The health study reveals that the exposure to arsenic has caused serious health hazard amongst the exposed population with pronounced skin manifestations, loss of appetite, anaemia, constipation, diarrhoea, general body weakness, raised blood pressure, breathlessness, diabetes, mental disabilities, diabetes, lumps in the body and few cancer incidences. It was found that 52% of the total collected groundwater samples had arsenic levels higher than the WHO limit of 10 µg/l (with a maximum arsenic concentration of 1212 µg/l) and the reduced arsenite was the predominant form in samples tested for speciation (N = 19). In the case of hair samples, 29% of the samples had arsenic concentrations higher than the permissible limit of 0.2 mg/kg, with a maximum arsenic concentration of 46 µg/l, while in 20% exposed population, there was significant arsenic contamination in urine samples > 50 µg/l. In Chapar village, the probability of carcinogenic-related risk in the exposed population consuming arsenic contaminated water is 100% for children, 99.1% for females and 97.3% for male subjects. The assessment report shared to the government enabled the village population to receive two arsenic filter units. These units are currently operational and catering 250 households providing arsenic-free water through piped water scheme. This study therefore identified a significant solution for this arsenic-exposed population.

The present study aims to carry out the assessment of arsenic contamination in groundwater samples along with the health status of the exposed population of Buxar district of Bihar. In the present study, randomly 80 groundwater samples were collected from the handpumps across the village households. For the health assessment, blood samples from human subjects were collected from the same household to know the status of the arsenic contamination in their body and were analysed. The study showed significantly very high arsenic contamination in their handpumps as well as in the blood samples of the exposed subjects. The maximum arsenic concentration observed in the handpump water sample was 1908 μg/L, while in blood sample of an individual was 462.1 μg/L. Cancer in 12 subjects was also observed within 2 years. The mitigation intervention was carried out by installing an arsenic filter plant for this arsenic exposed village population. After one year of the usage of the installed arsenic filter, there was significant reduction in the disease symptoms in the exposed population. The present study deciphers the groundwater status as well as the health status of the arsenic exposed population of a village of Bihar along with an mitigation approach to overcome the disease burden.

Arsenic poisoning through groundwater is the world’s greatest normal groundwater catastrophe which got an immense effect on worldwide general wellbeing. India is confronting the outcomes of arsenic poisoning in the zone of Ganga Brahmaputra alluvial plains. In Bihar, out of 38 districts, 18 districts are exceptionally influenced with groundwater arsenic defilement. In the present study, we have assessed the current situation of arsenic exposure in Sabalpur village of Saran district of Bihar after reporting of breast, renal, skin and thyroid cancer cases from this village along with typical symptoms of arsenicosis. Such cancer patients were identified at our institute and were taken for the study. The present investigation deals with the quantification of arsenic in groundwater, hair and nail samples of subjects as well as the survey of entire village to know the overall health status of the village people. A total of n=128 household handpump water samples as well as n=128 human hair and nail samples were collected from over n=520 households. Using the graphite furnace atomic absorption spectrophotometer (GF-AAS), all the samples were analysed. The investigation resulted that the 61% of the analysed samples particularly the groundwater had the arsenic levels more than the permissible limit of WHO (> 10 μg/L) with 244.20 μg/L as the highest arsenic contamination in one of the handpump water sample. The exposure effect of hair sample was worst as 88% of all the collected samples were having high arsenic levels more than the permissible limit (> 0.2 mg/Kg). In case of nail samples, 92% of the samples were having high arsenic concentration more than the permissible limit (> 0.5 mg/Kg). The health survey study revealed high magnitude of disease burden in the exposed population with symptoms such as asthma, anaemia, hepatomegaly, diabetes, cardiac problem, skin fungal infections, breathlessness and mental disability. Few cancer cases of renal, skin, breast and cervix were also found among the exposed population of this village. The percentage of cancer cases in this village was 0.94% that was low, but it would be an aggravated situation in the near future if people will continue drinking arsenic-contaminated water. Therefore, a mitigation intervention was carried out in March 2020 by installing an arsenic filter plant. The health situation in the village in the present scenario is hope to improve in the coming years. However, motivation and awareness among the village population are still required.

Abstract Globally, ~ 300 million people are exposed to arsenic poisoning while in India an estimated 70 million people are affected by consumption of arsenic contaminated water. The state of Bihar is an endemic belt for arsenic contamination in groundwater affecting over 10 million people with moderate to serious health manifestations. Life threatening disease like cancer is not uncommon now, and carcinoma type of cancer cases are on the rise. Breast cancer incidences in the state follows closely with more and more women getting affected. Approximately, 23% of the cancer types in women are related to breast cancer, diagnosed at a fairly advanced stage (III or IV) of the disease. The etiology of the disease is not clearly known though faulty lifestyle and genetic makeup cannot be ruled out. The present study attempts to derive a relation between increasing breast cancer cases with the sustained arsenic intake in the second most populated state of the country. Pathologically confirmed, female breast cancer patients (n = 55) from across the state were included in the study. Sampling of the breast tissue, blood, hair and toe nail was carried out by the surgical oncology department of the institute. As a part of cross-sectional study, (n = 12) female breast benign cases were taken as the control group and their biological samples were also collected. All the samples as per the protocol of NIOSH were digested and analysed by graphite furnace atomic absorption spectrophotometer. For the epidemiological parameter study, their age, type of malignancy, stage and demographic information was compiled. The results were correlated with the arsenic concentration in groundwater as per their endemic status and anomalous values on GIS platform. The role of geological studies to establish the morpho-stratigraphic control and aquifers with higher concentration was brought to use. The results are fairly indicative of the high correlation of anomalous concentration of arsenic with the sample population with diagnosed malignancy as compared to the control group. The maximum arsenic concentration observed in the biological samples in blood was 1856µg/L, in breast tissue 446.4µg/Kg, in hair 1296·9µg/Kg and in toenail 621·83µg/Kg respectively. The scattered plots correlate the relationship between age of the breast cancer patients with arsenic contamination, while the geospatial distribution positively correlates with the districts with increased arsenic endemicity in a predominantly alluvium dominated country. The high arsenic contamination in the biological samples of the breast cancer patients is an indicative marker to the possible relation of the disease to arsenic, as compared to the control population exposed to a much lesser toxicity. Consumption of water with more than 10 ppb arsenic contamination over a sustained longer time span has possibly exposed the population to a larger threat to disease as inferred from the findings. The disease breeding as a silent killer with reduced or unnoticeable symptoms upto a fairly advanced stage has further accentuated the problem. The present study thus endeavours to identify a significant relation of the disease with sustained intake of arsenic consumed through water and food products laden with anomalous concentration.

Reportedly, 300 million people worldwide are affected by the consumption of arsenic contaminated groundwater. India prominently figures amongst them and the state of Bihar has shown an upsurge in cases affected by arsenic poisoning. Escalated arsenic content in blood, leaves 1 in every 100 human being highly vulnerable to being affected by the disease. Uncontrolled intake may lead to skin, kidney, liver, bladder, or lung related cancer but even indirect forms of cancer are showing up on a regular basis with abnormal arsenic levels as the probable cause. But despite the apparent relation, the etiology has not been understood clearly. Blood samples of 2000 confirmed cancer patients were collected from pathology department of our institute. For cross-sectional design, 200 blood samples of subjects free from cancer from arsenic free pockets of Patna urban agglomeration, were collected. Blood arsenic levels in carcinoma patients as compared to sarcomas, lymphomas and leukemia were found to be higher. The geospatial map correlates the blood arsenic with cancer types and the demographic area of Gangetic plains. Most of the cancer patients with high blood arsenic concentration were from the districts near the river Ganges. The raised blood arsenic concentration in the 2000 cancer patients strongly correlates the relationship of arsenic with cancer especially the carcinoma type which is more vulnerable. The average arsenic concentration in blood of the cancer patients in the Gangetic plains denotes the significant role of arsenic which is present in endemic proportions. Thus, the study significantly correlates and advocates a strong relation of the deleterious element with the disease. It also underlines the need to address the problem by deciphering the root cause of the elevated cancer incidences in the Gangetic basin of Bihar and its association with arsenic poisoning.

Arsenic contamination in ground water is a serious and widespread global public health problem. It is estimated that more than 300 millions of population worldwide while about 180 million people in the Ganga–Meghna–Brahmaputra plains are exposed to arsenic poisoning. Out of 38 districts of Bihar, 18 are highly affected with ground water arsenic poisoning. A flood plain village of river Ganga Gyaspur Mahaji in Patna district was undertaken in the present study. The study deals with the survey of the entire village households with ground water arsenic quantification with special attention to know the health status of the arsenic-exposed population. The study revealed high arsenic concentration in the ground water of the village. The general health status of the village population was very poor as the subjects were exhibiting typical arsenicosis symptoms. Apart from this, they also had gastrointestinal problems, constipation, anaemia, loss of appetite, breathlessness, mental disability, etc. There were also reports of two cancer incidences from the village: one subject with squamous cell carcinoma of skin and the other with medullary breast cancer along with arsenicosis symptoms. The village population are getting infected and hence are at very high risk and may be impacted if they continue to drink arsenic-contaminated water in the future. Therefore, a proper strategy is urgently required for arsenic mitigation in this arsenic-exposed village through supply of safe drinking water.

Background: Over the last few decades there has been increased health related issues due to arsenic poisoning worldwide. In India, in state of Bihar, 18 districts are affected from arsenic poisoning causing various health related problems in the exposed population. Arsenic poisoning in Buxar district of Bihar in the recent times has been identified as one of arsenic hotspot of Bihar due to serious health related problems including cancer. Aims and Objectives: The present study aims to find out that whether arsenic contamination in groundwater causes impaired memory and intelligence in school children of Simri village of Buxar district of Bihar or not? Materials and Methods: In the present study, water samples were collected from three hand pumps, which were utilized by the school children for drinking purpose since last ten years. Hair samples of 65 students enrolled in this school were also collected for the analysis of arsenic concentration and its correlation with the drinking water arsenic was done. The same students were interviewed for neuro-behavioural and memory tests for which various methods were utilized like continuous performance test (CPT), symbol digit test (SDT), pattern memory test (PMT) and switching attention behavior (SAB). Results: The study revealed high arsenic concentration in the water and hair samples. The correlation between high arsenic concentration in water and hair denotes high degree of exposure. Their neuro-behavioural analysis reflected very alarming observations like impaired intelligence memory pattern along with the inattention, loss of concentration and alertness. The highest arsenic concentration in drinking water observed was 857 μg/L while in the children hair sample the maximum value was 12.609 mg/Kg. Conclusion: The present study thus concludes that arsenic poisoning is causing changes in the neuro-behavioural activities in school children of Simri village. Therefore, a specific strategy is urgently required to control the present problem.

Arsenic contamination in the groundwater is a serious and widespread global public health problem and India is one of the highly arsenic exposed country with maximum impact in the Ganga-Meghna-Brahmaputra (GMB) plains.A total of 18 districts out of 38 districts of the state of Bihar are highly affected with groundwater arsenic poisoning.Gyaspur-Mahaji village (a flood plain region of river Ganga) of Patna district was under taken for the study on the basis of large number of skin and breast cancer cases along with typical symptoms of arsenicosis diagnosed in Mahavir Cancer Institute and Research Centre, Patna.The study deals with the survey of the entire village with groundwater and blood arsenic estimation with special attention to know the health status of the arsenic exposed population.The study revealed high arsenic concentration in the groundwater in the village.Arsenic in the blood samples indicates biomarker for chronic arsenic exposure.The overall health status of the village people was very poor but the most unfortunate part was the appearance of skin cancer and breast cancer in many of the arsenic exposed population of this village.Although the number of such persons was few, it was still alarming as more persons may be impacted if they continue to drink arsenic contaminated water in future.

BACKGROUND:In the present times, arsenic poisoning contamination in the ground water has caused lots of health-related problems in the village population residing in middle Gangetic plain. In Bihar, about 16 districts have been reported to be affected with arsenic poisoning. For the ground water and health assessment, Simri village of Buxar district was undertaken which is a flood plain region of river Ganga. METHODS:In this study, 322 water samples were collected for arsenic estimation, and their results were analyzed. Furthermore, the correlation between arsenic contamination in ground water with depth and its distance from river Ganga were analyzed. Results are presented as mean ± standard deviation and total variation present in a set of data was analyzed through one-way analysis of variance. The difference among mean values has been analyzed by applying Dunnett's test. The criterion for statistical significance was set at P < 0.05. RESULTS:This study shows novel findings ever done in this area. Halwa Patti and Doodhi Patti strips were the most affected strips with high-arsenic concentration in hand pumps. Furthermore, a correlation between the arsenic concentration with the depth of the hand pumps and the distance from the river Ganga was also a significant study. CONCLUSIONS:The present study concludes that in Simri village there is high contamination of arsenic in ground water in all the strips. Such a huge population is at very high risk leading the village on the verge of causing health hazards among them. Therefore, an immediate strategy is required to combat the present problem.

OBJECTIVE:The main objective of the current study was to observe the ameliorative effect of Withania somnifera on arsenic-induced testicular toxicity by exploring the crucial parameters such as sperm counts, sperm motility, hormonal assay and lipid peroxidation including histopathology.MATERIALS AND METHODS:In the present study, arsenic in the form of sodium arsenite was administered orally to male Charles Foster rats for 45 days. Thereafter, ethanolic root extract of Withania somnifera was administered for 30 days to observe its ameliorative effect on male reproductive system.RESULTS:The study revealed that after administration of sodium arsenite, there was a decrease in the sperm counts and sperm motility accompanied by an increased incidence of sperm abnormalities and hormonal imbalance leading to infertility. However, after administration of Withania somnifera, there was significant reversal in the parameters denoting that it not only possesses antioxidant and rejuvenating property but also maintains the cellular integrity of testicular cells leading to normal functioning of it.CONCLUSION:The study concludes that Withania somnifera possesses phytoremedial effect. It is one of the best antidotes against arsenic-induced reproductive toxicity.