Effects of 6-nitro substitution on 5-methylchrysene tumorigenicity, mutagenicity and metabolism

Carcinogenesis. 1986 Apr;7(4):673-6. doi: 10.1093/carcin/7.4.673.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Chrysenes / toxicity*
  • Liver / metabolism
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Mice
  • Mutagenicity Tests
  • Phenanthrenes / toxicity*
  • Rats
  • Rats, Inbred F344
  • Skin Neoplasms / chemically induced
  • Structure-Activity Relationship

Substances

  • Chrysenes
  • Phenanthrenes
  • 6-nitro-5-methylchrysene
  • 5-methylchrysene