Generation of radical anions during NADPH reduction of four mutagenic and genotoxic alpha-nitro-arenofurans was examined. ESR showed that free radicals were generated during reduction solely in the presence of light. Computer simulations of ESR spectra were in good agreement with the experimental ones.

AbstractThe hydroxynaphthaldehydes (I) react with bromonitromethane (II) to give the nitronaphthopyrans (III).

7-methoxy-2-nitro-naphtho[2,1-b] furan (R 7000), known as a very potent mutagen and a very active in vivo carcinogen was employed here to develop squamous cell carcinoma in the rat. Seventy male Wistar rats received R 7000 p.o. dissolved in deionized water with 5% ethanol for periods from 1 to 21 months, while 20 served as controls receiving either water or 5% ethanol. All the animals were killed 21 months after the beginning of the experiment. Microscopic lesions were noticed in the forestomach after only 1 month of R 7000 administration. Histologic features varied from slight dysplasia to invasive carcinoma. Their sizes and invasive character increased significantly with the amount of R 7000 administered (P less than 0.05). R 7000 can be considered as a locally acting carcinogen since its carcinogenic effects appear at a place where the compound collects after swallowing. R 7000 is a weak carcinogen at the concentration employed here, when compared to some nitrosamines used in the development of forestomach cancer in rodents. The exact mechanism of the carcinogenic effects remains to be explained.

Nitro naphtofurans are powerful mutagenic agents. Subcutaneous injections of 7-methoxy 2-nitro naphtho [2,1-b] furan (R 7000) in C3H mice induce subcutaneous fibrosarcomas at the site of injection and squamous cell carcinomas of the stomach.

Among the nitro-naphthofurans, 7-methoxy-2-nitro-naphtho[2,1-b]furan (R 7000) has been proved to be a very potent mutagen. The purpose of this study was to demonstrate the carcinogenicity of a R 7000 to male Wistar rats initially 6 weeks old. R 7000 was dissolved in olive oil at a concentration of 1 mg/ml for injection. A S.C. injection of 0.5 ml containing 0.5 mg of R 7000 was given once a week in the neck of each animal tested. Ten control animals were not injected and 10 animals received a 0.5 ml injection of olive oil every week to serve as control. The remaining 70 animals were divided into five groups. Four groups of 10 animals received a total of either 2.5 mg, 5 mg, 7.5 mg or 10 mg of R 7000; the fifth group of 30 animals received 12.5 mg of R 7000. In animals which did not receive R 7000, no malignant tumor was observed. In those to whom R 7000 was administered tumors began to appear at the site of the injection after the third month. At the sixth month of the experiment, most of the animals injected had a tumor at the injection site. The number of tumor-bearing animals and the time between the first injection and the tumor appearance were closely related to the dose of R 7000 injected. These tumors were high grade fibrosarcomas, one animal developed a salivary fibrosarcoma. No other tumors or metastases were found in the autopsied animals. The high carcinogenicity of R 7000 in vivo is analogous to that of methylcholanthrene. The exact mechanism of action of 2-nitro-naphthofurans as carcinogens remains to be explained.

AbstractDie am Furanring methylierten Nitronaphthofurane (IIIa), (VIIIa), (IX) [analog (IIIa) aus 1‐Hydroxy‐ZZ‐acetyl‐naphthalin dargestellt; Ausb. 46% in der 1. und 26% in der 2. Stufe] und (XI) werden hinsichtlich ihrer antibakteriellen und grotozoiciden Aktivität mit ihren nicht methylierten Analogen verglichen.

2-nitro 7-methoxy naphtho [2,1-b] furan (R 7000) and 2-nitro 8-methoxy naphtho [2,1-b] furan, which are highly mutagenic on the bacterium Salmonella typhimurium have little activity on the yeast Saccharomyces cerevisiae. Nevertheless, irradiation at 365 nm elicits a weak but significant increase of their mutagenic activity on this yeast.

The cytostatic effect of various derivatives of 2-nitro-naphthofurans has been determined in vitro on L1210 leukemia cells. A recently described new bio-assay (Discotest) was used, which consists in plating the cells in soft agarose and placing on top of the agarose layer a paper disc soaked with the compound to be tested. The halo of inhibition of colony formation which results from diffusion of the compound is proportional to the logarithm of the compound concentration. The most active derivatives were the 2-nitro-7-methoxy and 2-nitro-8-methoxy-naphtho[2,1-b] furans which are known to be highly bactericidal and protozoocidal.