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.
Bibliographical noteFunding Information:
We wish to thank Maria Valentine for excellent technical assistance. We are especially grateful to Ik Peter P.Fu at the National Center for Toxicological Research, Jefferson, AR for assistance in obtaining the 500 MHz p.m.r. spectrum of 6-nitr8-5-methylchrysene. We also acknowledge the use of the NTC Wide Bore Spectrometer at the Rockefeller University. The spectrometer was purchased with funds from the National Science Foundation (PCM-7912083), the Camille and Henry Dreyfus Foundation and the Fleischman Foundation. A study of Chemical Carcinogenesis, 96. This work was supported by NCI Grants CA-35519 and CA-32242.