Effects of 6-nitro substitution on 5-methylchrysene tumorigenicity, mutagenicity and metabolism.
6-Nitro-5-methylchrysene was prepared by nitration of 5-methylchrysene and the mutagenic and tumorigenic activities of the two compounds were compared. Whereas 5-methylchrysene was a strong tumor initiator on mouse skin, no tumors were observed in the mice treated with 6-nitro-5-methylchrysene. In Salmonella typhimurium TA100, both compounds were mutagenic in the presence, but not in the absence, of rat liver 9000 g supernatant. The major metabolite of 6-nitro-5-methylchrysene in rat liver in vitro was trans-1,2-dihydro-1,2-dihydroxy-6-nitro-5-methylchrysene. In view of the ready conversion of 6-nitro-5-methylchrysene to a 1,2-dihydrodiol, its apparent lack of tumorigenicity in mouse skin was intriguing.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002911:Chrysenes / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D009152:Mutagenicity Tests; D010616:Phenanthrenes / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012878:Skin Neoplasms / Q000139:chemically induced; D013329:Structure-Activity Relationship
D002911:Chrysenes; D010616:Phenanthrenes; C048586:6-nitro-5-methylchrysene; C008422:5-methylchrysene