8-Nitroquinoline

Reversibility of forestomach lesions induced by genotoxic and non-genotoxic carcinogens was compared histopathologically. Groups of 30 to 33 male F344 rats were given dietary 0.1% 8-nitroquinoline, dietary 0.4-0.2% 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, an intragastric dose of 20 mg/kg body weight N-methyl-N'-nitro-N-nitrosoguanidine once a week, or 20 ppm N-methylnitrosourethane in the drinking water as a genotoxic carcinogen, or 2% butylated hydroxyanisole, 2% caffeic acid, 2% sesamol or 2% 4-methoxyphenol in the diet as a non-genotoxic carcinogen for 24 weeks. Ten or 11 rats in each group were killed at week 24. Half of the remainder were maintained on basal diet alone for an additional 24 weeks and the other half were given the same chemical for 48 weeks, and then killed. Forestomach lesions induced by genotoxic carcinogens did not regress after removal of carcinogens. In contrast, simple or papillary hyperplasia (SPH), but not basal cell hyperplasia (BCH), induced by non-genotoxic carcinogens clearly regressed after cessation of insult. SPH labeling indices in the non-genotoxic carcinogen-treated cases decreased after removal of the carcinogenic stimulus whereas BCH values were low irrespective of treatment. Atypical hyperplasia (AH), observed at high incidences in rats treated with genotoxic carcinogens, was also evident in animals receiving non-genotoxic agents, even after their withdrawal, albeit at low incidences. AH labeling indices remained high even without continued insult. These results indicate that even with non-genotoxic carcinogens, heritable alterations at the DNA level could occur during strong cell proliferation and result in AH development. This putative preneoplastic lesion might then progress to produce carcinomas.

Syrian golden hamsters were administered 8-nitroquinoline, at a concentration of 0.05%, in a 10% ethanol solution as drinking water for 104 weeks. The animals were kept under observation until 112 weeks of age when the experiment was terminated. Both control and treated groups developed tumors in a pattern indistinguishable from that usually observed in Syrian golden hamsters. Thus the result of this experiment indicates that 8-nitroquinoline given orally at a concentration of 0.05% is not carcinogenic in Syrian golden hamsters.

In Ames test, the quinoline derivatives, 6-nitroquinoline (6-NQ), 8-nitroquinoline (8-NQ), 6-methylquinoline (6-NQ), 8-methylquinoline (8-MQ) and 8-hydroxyquinoline (8-HQ) are mutagenic, whereas 5,7-dibromo-quinoline (5,7-DQ) is not. These compounds were administered to groups of male and female F344 rats in their diet for 104 weeks. 8-NQ induced forestomach tumors in male and female rats: it induced squamous cell papillomas in 28 (93.3%) of 30 males and in 36 (97.3%) of 37 females, and squamous cell carcinomas in 20 (66.7%) of 30 males and 24 (64.9%) of 37 females. Thus there was no sex difference in its carcinogenicity. 6-NQ induced only focal hyperplasia of the forestomach at an incidence of 30.0% in male rats and 52.8% in female rats. These results indicate a discrepancy between the mutagenicities of quinoline derivatives and their carcinogenicities to rats: only 8-NQ was carcinogenic to F344 rats.

8-Nitroquinoline was added to the semisynthetic diet of outbred Sprague-Dawley rats for 48 weeks. Squamous cell carcinomas of the upper digestive tract (tongue and esophagus), but especially of the forestomach, occurred among the higher concentration groups. Squamous cell carcinoma of the forestomach occurred in 3 of 11 (27.3%) rats in the 2500 ppm group and 7 of 35 (20.0%) rats in the 1000 ppm group. Three cases of lung adenoma were also observed in the 2500 ppm group. Results clearly indicate that 8-nitroquinoline is carcinogenic in rats when administered orally in a semisynthetic diet.