The mutagenic activities in Salmonella typhimurium and tumorigenic activities in newborn mice of 6-nitrochrvsene (6-NC), 5-methyl-6-nitrochrysene (5-Me-6-NC), 11-methyl-6-nttrochrysene (11-Me-6-NC) and 5-methylchrysene (5-MeC) were compared. In S.typhimurium TA100 in the absence of rat liver 9000 g supernatant, 11-Me-6-NC was the most active compound followed by 6-NC; 5-Me-6-NC and 5-MeC were inactive. In the assays conducted in the presence of rat liver 9000 g supernatant, the order of activity was 11-Me-6-NC < 6-NC < 5-Me-6-NC ̃ 5-MeC. In S.typhimurium TA98 a similar trend was observed. For the tumorigenicity studies, groups of mice were treated with the appropriate compounds in DMSO by i.p. injections on the 1st, 8th and 15th day of life. At a dose of 100 nmol/mouse 6-NC induced significantly more lung tumors than 5-MeC, which in turn was more active than 11-Me-6-NC and 5-Me-6-NC. All compounds induced significant numbers of liver tumors in treated males compared to controls; the order of activity was the same as that observed for lung tumor induction. The results of this study clearly indicate that bay region methyl substitution can either inhibit (5-position) or enhance (11-position) the mutagenic activity of 6-NC. In contrast, bay region methyl substitution (5- and 11-positions) inhibited the tumorigenic activity of 6-NC in newborn mice. Since ring oxidation and nitroreduction are involved in the metabolic activation of 6-NC in newborn mice, bay region methyl substitution may either inhibit the nitroreduction pathway or hinder the formation of the appropriate bay region diol epoxide. Sterk factors may be important in determining the tumorigenicity of methylated nitrochrysenes.
Bibliographical noteFunding Information:
We thank Barbara Way for performing the mutagenicity assays and Joanne Braley for animal care, maintenance and treatments. We also acknowledge the help of Dr Pramod Upadhyaya and Dr Desai Dhimant. This study was supported by National Cancer Institute Grant CA35519. This is paper no. 126 of the series 'A study of chemical carcinogenesis'.
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