The activation and DNA binding of 7-methylbenz[c]-acridine catalysed by mouse liver microsomes

The metabolism of the carcinogen, 7-methylbenz[c]acridine (7MBAC), in liver microsomes prepared from untreated, and phenobarbital sodium (PB) and 3-methylcholanthrene (MC) induced male C57BL/6 mice was examined by high pressure liquid chromatography (HPLC). The abilities of control and MC induced liver microsomes to catalyse covalent binding of the carcinogen to DNA were comparable (60 pmol 7MBAC bound/mg DNA), although this maximum binding level observed was achieved at different 7MBAC concentrations for control (100 microM) and MC induced (25 microM) preparations. In vivo binding of 7MBAC to liver DNA was greater than that observed for lung DNA of the same animals but over 21 h bound 7MBAC levels decreased to a greater extent in liver than in lung. One fraction of a digest of in vitro alkylated DNA gave a fluorescence emission spectrum very similar to that of 7-methyl-1,2,3,4-tetrahydrobenz[c]acridine. This result suggests that diol epoxides functionalised at the 1,2,3,4-positions may be ultimate carcinogens derived from 7MBAC.