Background Extramural venous invasion (EMVI) is a prognostic factor in rectal cancer. There are two types: EMVI detected by magnetic resonance imaging (MRI) (mr-EMVI) and EMVI detected by pathology (p-EMVI). They have been separately evaluated, but they have not yet been concurrently evaluated. We therefore evaluate both mr-EMVI and p-EMVI in rectal cancer at the same time and clarify their association with prognosis. Patients and Methods Included were the 186 consecutive patients who underwent complete radical resection of tumors ≤ stage III at Wakayama Medical University Hospital, Japan, between 2010 and 2018. All underwent preoperative MRI examination, and were reassessed for EMVI by a radiologist. Surgically resected specimens were then reassessed for EMVI by a pathologist. We assessed the correlation between positivity of mr-EMVI and p-EMVI and prognosis, and the clinicopathological background behind them. Results Patients with double negativity for mr-EMVI and p-EMVI had better prognosis than patients with mr-EMVI or p-EMVI positivity ( p < 0.0001). Positivity for mr-EMVI or p-EMVI was a poor independent prognostic factor in multivariate analysis. Conclusions Combined analysis of mr-EMVI and p-EMVI may enable prediction of postoperative prognosis of rectal cancer. Patients with double negativity of mr-EMVI and p-EMVI had better prognosis than patients with some form of positivity. Stated differently, patients with positivity of mr-EMVI, p-EMVI, or both had a poorer prognosis than those with double negativity. Postoperative adjuvant chemotherapy may improve poor prognosis. Combined evaluation of mr-EMVI and p-EMVI may be used to predict clinical outcomes and may be an effective prognostic predictor of rectal cancer.

Aims Haemangioblastomas arise in the central nervous system. Rarely, haemangioblastomas may develop in extra‐neural sites, such as the kidneys. A few reported cases of renal cell carcinomas (RCCs) with haemangioblastoma‐like features have exhibited both clear cell renal cell carcinoma (CCRCC)‐ and haemangioblastoma‐like components. The clinicopathological and molecular characteristics of RCCs with haemangioblastoma‐like features were analysed, focusing on VHL alterations, in comparison with CCRCCs partially resembling haemangioblastoma. Methods and Results Four RCCs with haemangioblastoma‐like features and five CCRCCs partially resembling haemangioblastoma were included. The RCCs with haemangioblastoma‐like features were indolent and lacked adverse prognostic factors. All RCCs with haemangioblastoma‐like features had a well‐circumscribed appearance and a thick fibromuscular capsule, with fibromuscular bundles extending into the tumour to varying degrees in the three tumours. Each RCC with haemangioblastoma‐like features exhibited CCRCC‐like areas with indistinct tubular structures and foci of haemangioblastoma‐like areas, in which vessels and short spindle cells overwhelmed tumour cells. Whereas haemangioblastoma‐like areas in the CCRCCs partially resembling haemangioblastoma exhibited sparse vessels and spindle cells and distinct clear cells. The RCCs with haemangioblastoma‐like features exhibited a unique immunohistochemical profile, with positive staining for inhibin‐α, S100, carbonic‐anhydrase‐9, keratin7, and high molecular weight keratin and negative staining for (alpha‐methylacyl‐CoA racemase) AMACR. RCC with haemangioblastoma‐like features did not display any VHL alterations, including VHL mutation, 3p LOH, and methylation of the VHL promoter region, and the two tumours harboured a likely oncogenic missense variant of MTOR (c.7280T>G). Conclusion The histopathological, immunohistochemical, and molecular findings suggest that RCC with haemangioblastoma‐like features is a distinct entity from CCRCC.

Abstract Background Low‐grade serous carcinoma (LGSC) of the ovary, which is extremely rare tumor, has better prognosis than high‐grade serous carcinoma (HGSC). Genetic backgrounds of those are different, so that LGSC usually shows KRAS or BRAF mutation, whereas HGSC does not show such mutations. Since treatment strategies of those are different, differential pathological diagnosis between LGSC and HGSC is very important. Case We report a case of LGSC that was diagnosed by both cytological findings and genetic analysis using small amount cells from cytological specimen. The 30‐year‐old Japanese woman with bilateral ovarian tumors underwent salpingo‐oopherectomy. The peritoneal washing cytologic specimen and touched cytologic specimen from the tumor included non‐complex clusters with psammoma bodies composed of tumor cells with mild to moderate atypia and without bizarre nuclei. The ovarian tumor was histologically diagnosed as LGSC. The genetic analysis that was done using exfoliated cells from peritoneal washings specimen by idensy™, detected KRAS mutation at codon 12/13. Conclusion The genetic investigation using cytological specimen as well as characteristic cytological findings were useful to make differential diagnosis between LGSC and HGSC.

Background: Although several molecular analyses have shown that the Kras gene status is related to long-term survival of patients with pancreatic ductal adenocarcinoma (PDAC), the results remain controversial. Here, we examined the Kras gene status in a cohort of unresectable PDAC patients who underwent first-line therapy with gemcitabine and nab-paclitaxel (GA) and assessed differences in chemotherapy responses and survival. Methods: Patients with a histological diagnosis of PDAC (based on EUS-guided fine-needle aspiration) from 2017 to 2019 were enrolled. Tumor genomic DNA was extracted from residual liquid-based cytology specimens and Kras mutations were assessed using the quenching probe method. The relationships between the Kras status and progression-free survival (PFS) and overall survival (OS) were assessed. Results: Of the 110 patients analyzed, 15 had wild-type Kras. Those with the wild-type gene showed significantly longer PFS and OS than those with mutant Kras (6.9/5.3 months (p = 0.044) vs. 19.9/11.8 months (p = 0.037), respectively). Multivariate analyses identified wild-type Kras as a significant independent factor associated with longer PFS and OS (HR = 0.53 (p = 0.045) and HR = 0.35 (p = 0.007), respectively). Conclusions: The analysis of the Kras gene status could be used to predict therapeutic responses to GA and prognosis in unresectable PDAC patients.

〈Background〉 We reported on the characteristics of green tea extract (GTE)-induced hepatotoxicity in rats. Using this model, we explored the inhibitory effects of n-9 PUFA, mead acid (MA), by dietary supplementation. 〈Methods〉 7-week-old male Sprague-Dawley rats received a single intraperitoneal injection of 200 mg/kg GTE, serum and liver were collected 24, 48 hrs, and 7 days after the GTE injection. The control or 4.8% MA diets was given from one week before GTE injection to sacrifice. Control diet + saline, 4.8% MA diet + saline, control diet + GTE, and 4.8% MA diet + GTE groups were set. Serum biomarkers of hepatotoxicity [aspartate aminotransferase (AST), alanine aminotransferase (ALT)], liver histopathology, and immunohistochemistry of apoptosis (γH2A.X), oxidative stress (8-nitroguanosine) and hypoxia [hypoxia inducible factor (HIF)-1α] were examined. Fatty acid in serum and liver tissue of the control diet + saline and 4.8% MA diet+ saline groups were analyzed. 〈Results〉 In the control diet + GTE group, AST and ALT levels increased. Centrilobular hepatocellular necrosis was seen 24 and 48 hrs after GTE exposure. Furthermore, the levels of these changes decreased in the MA diet group. In the control diet + GTE group, γH2A.X, 8-nitroguanosine, and HIF-1α-positive hepatocytes appeared and peaked at 48 hrs. The level of these changes reduced by MA diet feeding. MA composition in the serum and liver significantly increased in the MA diet group, compared to the control diet group. 〈Conclusion〉The levels of GTE-induced liver damage, such as serum biomarkers, histology, and immunohistochemistry for hepatotoxicity were inhibited by MA diet feeding. This effect may be related to suppression of cell death via the pathway of oxidative stress and hypoxia in the liver.

A mode of action of acetaminophen （APAP）-induced renal toxicity is supposedly via N-acetyl-p-benzoquinone imine. In this renal toxicity model we explored the inhibitory effects of mead acid （MA）, which is an n-9 PUFA of dietary supplementation. Seven week-old male SD rats received a single intraperitoneal injection of 500 mg/kg APAP and serum and kidney samples were collected at 24 and 48hrs after. Basal or 4.8% MA diets were given from one week before the APAP injection until sacrifice. Experimental groups were basal diet + vehicle, 4.8% MA diet + vehicle, basal diet + APAP, and 4.8% MA diet + APAP. Biomarkers of renal toxicity （blood urea nitrogen （BUN）, creatinine （CRE））, histopathology of kidney and immunohistochemistry for drug-metabolizing enzyme （cytochrome P4502E1（CYP2E1）） and oxidative stress （heme oxgenase （HO-1）, thymidine glycol （TG）） were performed. The diacron-reactive oxygen metabolites （d-ROMs） and bioantioxidant power （BAP） tests were conducted to detect oxidative stress and anti-oxidative activity in serum, respectively. In the basal diet+ APAP group, the BUN and CRE levels were significantly increased and acute necrosis and dilatation in the renal outer medullary area were present. Tubular necrosis was detected mainly in proximal tubules which was positive for CYP2E1. HO-1 and TG signals were also seen in these epithelia. In contrast, these tubular changes and expression of HO-1signal were reduced in the rats fed the MA diet. MA supplementation inhibited APAP induced renal toxicity via the decreased level of oxidative stress in kidney.

In the present study, the therapeutic effects of dietary supplemental mead acid (MA), an n-9 polyunsaturated fatty acid, was tested in two different acute liver injury rat models. Six-week old Sprague Dawley rats were given basal diet with and without 4.8% MA. One-week later control rats remained on their basal and 4.8% MA diets while treated rats on basal and 4.8% MA diet received a single intraperitoneal injection of 2 mL/kg carbon tetrachloride (CCl4) or 500 mg/kg acetaminophen (APAP). Serum and liver samples were collected 48hrs after CCl4 or APAP injection. Serum biomarkers of hepatotoxicity (aspartate aminotransferase (AST), alanine aminotransferase (ALT) and total bilirubin (T-BIL)), histopathology, and immunohistochemistry for oxidative stress were examined. Fatty acids in total lipids were also analyzed. Biomarker levels were decreased in the CCl4-or APAP- injected 4.8% MA diet groups compared to the CCl4-or APAP- injected basal diet groups. In serum and liver, the concentration of MA was significantly higher in the MA diet group as compared to controls. Our experimental results demonstrate that MA reduced the severity of liver injury in these models by its antioxidant activity.

Acquired cystic disease of kidney–associated renal cell carcinoma (ACD-RCC) is a distinct subtype of renal cell carcinoma with unique morphologic and clinicopathologic features. Generally, ACD-RCC is regarded as an indolent tumor; however, prognostic and outcomes data have been conflicted by the limited and relatively low number of cases with patient follow-up or adverse events. In this study, we focused on the histology of metastatic lesions and identifying prognostic factors associated with metastatic progression. From 32 cases in the cohort, 9 patients had metastasis [ACD-RCC (M+)] and 23 patients were without metastasis [ACD-RCC (M−)]. The median age of patients was 52 years; right side, n=10; left side, n=18; bilateral, n=4; median tumor size=2.6 cm; median hemodialysis duration=17 y; and the median duration of follow-up was 50 mo. Immunohistochemistry showed ACD-RCC to be racemase positive and CK7 negative to focally positive within tumor cells, with consistent positivity for renal histogenesis-associated markers (PAX8 and RCC antigen); S100A1 was a less reliable marker at metastatic sites. All metastatic ACD-RCC except 2 cases involved lymph nodes (para-aortic, renal hilar, subclavicular). Overall, 6/9 (67%) had visceral metastasis to sites including lung (n=3), liver (n=3), bone (n=5), stomach (n=1), and brain (n=1). In total, 5/9 (56%) metastatic tumors had distinctive cystic growth pattern at the metastatic site; intriguingly metastatic tumors had intrametastatic oxalate crystal deposition, a pathognomonic feature associated with primary tumors. Four of nine (44%) patients with ACD-RCC (M+) had fatal outcomes due to metastatic disease. Clinically significant adverse prognostic features associated with metastasis [median follow-up 47 mo, ACD-RCC (M+) vs. ACD-RCC (M−), 50 mo] included: duration of hemodialysis (≥20 vs. <20 y, P=0.0085) and tumor necrosis (P=0.049). Because of sufficient overlap between these parameters, the study was not able to identify parameters that would be reliable in further management strategies, in clinical settings. Our data indicate that ACD-RCC is a tumor which has distinct metastatic potential with nodal and visceral tropism and proclivity for cystic morphology at metastatic sites; this is the first report of the presence of oxalate crystals in metastatic tumors. Our data suggest that ACD-RCC patients with prolonged hemodialysis and tumoral coagulative necrosis require additional surveillance in view of the association of these parameters with metastatic progression.

In the present study, the dietary effects of mead acid (MA; 5,8,11‑eicosatrienoic acid) on 7,12‑dimethylbenz[a]anthracene (DMBA)‑induced breast cancer in female Sprague‑Dawley rats were examined. The 2.4 and 4.8% MA diets were commenced when the rats were 6 weeks of age. DMBA was administered by a single oral ingestion when the rats were 7 weeks of age, and the rats were maintained on the respective diets until 19 weeks of age. Tumor weight, histopathology, cell kinetics, and the fatty acid composition in breast tissue and serum were examined. In the control (CTR) group, the DMBA‑exposed rats were fed a basal diet (0% MA). The results revealed that there were no significant differences in tumor incidence, cell kinetics and in the N‑6/N‑3 ratio in breast tissue between the groups. Only the N‑6/N‑3 ratio of fatty acid composition in serum was significantly decreased in the 2.4% MA diet group. In previous studies, the 2.4% MA diet was shown to suppress N‑methyl‑N‑nitrosourea‑induced luminal A mammary cancer by decreasing cancer cell proliferation. The findings of the present study differ from those of previous studies with different breast cancer models. To further clarify the effects of MA against breast carcinogenesis, further investigations with different experimental breast cancer models are recommended.

The diagnosis of patients with malignancies relies on the results of a clinical cytological examination. To enhance the diagnostic qualities of cytological examinations, it is important to have a detailed analysis of the cell’s characteristics. There is, therefore, a need for developing a new auxiliary method for cytological diagnosis. In this study, we focused on studying the charge of the cell membrane surface of fixed cells, which is one of important cell’s characteristics. Although fixed cells lose membrane potential which is observed in living cells owing to ion dynamics, we hypothesized that fixed cells still have a cell membrane surface charge due to cell membrane components and structure. We used 5 cell lines in this study (ARO, C32TG, RT4, TK, UM-UC-14). After fixation with CytoRich Red, we measured the cell membrane surface charge of fixed cells in solution using zeta potential measurements and fixed cells on glass slides, visualizing it using antibody-labeled beads and positively-charged beads. Furthermore, we measured the cell membrane surface charge of fixed cells under different conditions, such as different solution of fixative, ion concentration, pH, and pepsin treatments. The zeta potential measurements and visualization using the beads indicated that the cell membrane surface of fixed cells was negatively charged, and also that the charge varied among fixed cells. The charge state was affected by the different treatments. Moreover, the number of cell-bound beads was small in interphase, anaphase, and apoptotic cells. We concluded that the negative cell membrane surface charge was influenced by the three-dimensional structure of proteins as well as the different types of amino acids and lipids on the cell membrane. Thus, cell surface charge visualization can be applied as a new auxiliary method for clinical cytological diagnosis. This is the first systematic report of the cell membrane surface charge of fixed cells.

BACKGROUND:Intraoperative diagnosis is an essential tool for the rapid diagnostic assessment of clinically critical head and neck lesions. Thus, we assumed that a combination of frozen section histological and cytological diagnoses may be preferable. Here, we investigated a relatively new method called liquid-based cytology of rinsed tissue fragments (LBC-RTF) and compared this method with intraoperative histological diagnosis.METHODS:We used 68 tissue biopsies (9 brains, 8 lymph nodes, 22 salivary glands, and 29 thyroid samples). Samples submitted for intraoperative consultation were divided into two-halves: one was used to prepare frozen sections, and the other was prepared for LBC-RTF by washing with PreservCyt. We then compared the final diagnosis obtained from permanent sections with the intraoperative histological diagnosis based on frozen sections and examination of LBC-RTF preparations.RESULTS:The accuracy of LBC-RTF was higher than that of intraoperative histological diagnosis alone, based on frozen sections of every organ (LBC-RTF: 91.2% vs intraoperative histological diagnosis: 80.9%). With LBC-RTF, artifacts that are commonly observed in frozen sections were not present. In addition, even with challenging cases from which it is impossible to prepare frozen sections, intraoperative diagnosis was possible using the LBC-RTF technique.CONCLUSION:Both histological and cytological intraoperative diagnoses were possible during a surgery if the LBC-RTF technique was used. Moreover, our findings suggest that LBC-RTF improved the diagnostic accuracy of traditional intraoperative diagnosis.

To assess the toxicological and pharmacological effects of chemicals, it is important to know what kinds of neoplasms naturally occur in the early life of laboratory animals. In the present study, we identified three spontaneous hematopoietic tumors in three of 52 young female Sprague-Dawley rats used in a pharmacological study. These cases included two rats (Case 1 and 2) from a sesame oil-treated group and one rat (Case 3) from a chemical-treated group in the same single gavage study. Case 1 rapidly lost body weight at 13 weeks of age without any clinical signs and died. Round lymphoid tumor cells were found in the spleen, liver, bone marrow, and pancreas. The tumor cells were immunohistochemically positive for CD3 and PCNA, which is suggestive of malignant T-cell lymphoma. Cases 2 and 3 had rapid body weight loss at 14 and 16 weeks of age, respectively, exhibited severe anemia, hypolocomotion, and decreased body temperature, and were euthanized due to a poor prognosis based on severe clinical signs. Pleomorphic large tumor cells were found in the spleen, liver, bone marrow, lymph nodes, heart, kidneys, lung, pancreas, adrenal glands, pituitary gland, ovaries, Harderian gland, and/or eyes. The tumor cells were immunoreactive for CD34, lysozyme, and PCNA, which is suggestive of myeloid leukemia. These cases might provide useful historical control information for rat toxicity studies.

The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N-nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor α (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans.

N-methyl-N-nitrosourea (MNU) possesses peripheral nervous system carcinogenic activity in rats and induces benign and malignant schwannomas in systemic organs. In this retrospective study, we compared the characteristics of various immunohistochemical markers in MNU-induced schwannomas in male Crj:CD(SD)IGS rats including: vimentin (Vim), S100, p75 nerve growth factor receptor (LNGFR), CD57, pancytokeratin (CK), myoglobin, desmin and α smooth muscle actin (SMA). Single intraperitoneal exposures of 50 or 75mg/kg MNU in male rats at the age of 4 weeks induced schwannomas in 43 surviving and terminated rats up to 30-weeks-old. The incidence rate of neoplastic lesions was 37% (16 of 43 rats). Benign schwannomas (mesentery, pancreas, thymus) and malignant schwannomas (subendocardium, cardiac intramural, thoracic cavity, abdominal cavity, prostate), occurred in nine and seven rats, respectively. All neoplastic lesions were moderately or strongly positive for Vim, S100 and LNGFR proteins. Benign tumors were weakly positive and malignant tumors strongly positive for Ki-67, suggesting a high active proliferation rate of Schwann cell precursors. All lesions were negative for CD57, CK, myoglobin, desmin and SMA. This data may provide useful immunohistochemical information for the investigation of schwannomas in rat chemical carcinogenicity studies.

BACKGROUND Natural xanthophylls, canthaxanthin and astaxanthin are known to exhibit anticancer activity. However, the dietary effects of canthaxanthin and astaxanthin on N-methyl-N-nitrosourea (MNU)-induced mammary cancer remain controversial, and their mechanisms of action have not been clearly identified. MATERIALS AND METHODS Three-week-old female Sprague-Dawley rats were fed a xanthophyll-free (basal diet) diet or experimental diets containing canthaxanthin or astaxanthin (0.04% and 0.4%) for 5 weeks (until 8 weeks of age), after which all rats were provided the basal diet (n=15 each). Rats were administered MNU at 6 weeks of age, and the incidence of mammary tumors at 20 weeks of age was compared. The expression of adiponectin in mammary adipose tissues taken at 7 weeks of age was also compared. RESULTS Compared to the basal diet group, the 0.4% (but not the 0.04%) astaxanthin diet significantly reduced the incidence of palpable mammary carcinoma (92% vs. 42%; p<0.05), while the low and high canthaxanthin diets produced no significant inhibition. Adiponectin immunoblotting showed significantly higher expression in the 0.4% astaxanthin diet group, while the other groups were similar to the basal diet group. CONCLUSION High concentrations of astaxanthin suppress MNU-induced mammary carcinoma. Changes in adiponectin may be involved in the mechanism of action.

Most uterine cervix adenocarcinomas are primary tumors. Here, we report a case of pancreatic cancer that metastasized to the uterine cervix. The patient was a 77-year-old Jehovah's Witness whose pancreatic cancer had been diagnosed 10years previously. As she had refused blood transfusion on religious grounds, the tumor only underwent segmental excision, followed by radiofrequency wave therapy and chemotherapy. During a routine health examination 6years after her pancreatic tumor resection, a tumor in the left lower lobe of her lung was found, and then removed. Three years after the lung surgery, her serum CA19-9 increased. A detailed examination found tumors in the ascending colon and uterine cervix. She underwent chemotherapy and radiotherapy after a right hemicolectomy, endocervical biopsy, and endocervical cytology. At present, about 10years after her initial diagnosis, she is alive with no recurrence or metastatic findings. Morphologically, well-differentiated pancreatic adenocarcinoma is similar to endocervical type adenocarcinoma and adenocarcinoma in situ of the uterine cervix. Therefore, careful immunohistochemical examination and clear understanding of the patient's clinical information are needed in diagnosing adenocarcinoma in the uterine cervix.

A single intraperitoneal injection of 50 or 75 mg/kg N-methyl-N-nitrosourea in male Sprague-Dawley rats at 4 weeks of age, dose-dependently resulted in cutaneous epithelial cysts and tumors of pilosebaceous origin. Cysts were composed of epidermal cysts or mixed epidermal and inner root sheath hybrid cysts. The majority of induced tumors were keratoacanthomas. A few tumors were trichofolliculomas, trichoblastomas, pilomatricomas, or sebaceous adenomas. All tumors were benign pilosebaceous tumors. Keratoacanthomas were crater-shaped tumors with thick infoldings of epithelium containing keratohyalin granules (epidermal lip) that abruptly changed to epithelium containing trichohyalin granules. The morphological similarity and resemblance of keratin 1, 10, and 14 profiles, and p63 and β-catenin expression between mixed epidermal and inner root sheath hybrid cysts and keratoacanthomas suggests that hybrid cysts progressed to keratoacanthomas, and the cells from infundibular cells to inner root sheath cells of the pilar segment seem to be the origin of rat keratoacanthomas. Immunohistochemical localization of keratins 1, 10 and 14, p63, and β-catenin in trichofolliculoma, trichoblastoma, and pilomatricoma, as well as keratoacanthoma, may indicate tumor histogenesis.

The effects of green tea extract (GTE) on N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell apoptosis were examined, and the possible mechanisms of action of GTE were assessed. Alterations in the retinal morphological architecture were determined by hematoxylin-eosin staining, vimentin immunoreactivity, and photoreceptor cell apoptosis (TUNEL labeling). Expression of oxidant marker, heme oxygenase (HO)-1, mRNA levels in outer nuclear cells was assessed by laser capture microdissection (LCM). Sprague-Dawley rats were given 40 mg/kg MNU at 7 weeks of age in the absence and presence of 250 mg/kg GTE treatment (once daily from 3 days prior to MNU for a maximum 10 days). Although photoreceptor cell degeneration began 24 hr after MNU, the morphological effects of GTE at the time point were not definitive. However, GTE lowered TUNEL labeling and HO-1 mRNA expression. At 7 days after MNU, photoreceptor damage was attenuated by GTE treatment. Therefore, the ability of GTE to reduce MNU-induced photoreceptor cell apoptosis may be due to its antioxidant properties.

To evaluate the potential role of genetic background in the susceptibility to retinal degeneration induced by N-methyl-N-nitrosourea (MNU), female rats of the Sprague-Dawley (SD), Long-Evans (LE) and Copenhagen (CH) strains were administered 50 mg/kg MNU or saline at 7 weeks of age. Retina morphology and morphometric analysis of all rats was performed 7 days after MNU administration. Atrophy of both the peripheral and central outer retina occurred in all rat strains exposed to MNU. Decreased photoreceptor cell ratio and increased retinal damage ratio were observed. The severities of the retinal atrophy were similar among all three rat strains. In conclusion, MNU-induced photoreceptor degeneration developed consistently in all three strains regardless of the absence (SD rats) or presence (LE and CH rats) of melanin in the retina, suggesting that genetic and melanin factors did not affect photoreceptor cell death after MNU.