Formation of 7-hydroxymethyl-12-methylbenz(a)anthracene-DNA adducts from 7,12-dimethylbenz(a)anthracene in mouse epidermis.
The formation of DNA adducts from [3H]-7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA) and [3H]-7,12-dimethylbenz(a)anthracene (DMBA) in the epidermis of Sencar mice was analyzed. Comparison of Sephadex LH-20 chromatographic profiles of DNA samples isolated from mice treated with DMBA or 7-OHM-12-MBA suggested that the DMBA-treated animals contained DNA adduct(s) derived from the further metabolism of 7-OHM-12-MBA. Further analysis of DNA samples from DMBA-treated mice by high-pressure liquid chromatography demonstrated the presence of 5 DNA adducts which were chromatographically indistinguishable from the DNA adducts formed in 7-OHM-12-MBA-treated mice. Epidermal homogenates were utilized to catalyze the covalent binding of [3H]DMBA and [3H]-7-OHM-12-MBA to calf thymus DNA in vitro. Under conditions of limiting concentrations of [3H]DMBA, the majority of the DNA adducts formed chromatographed in regions where 7-OHM-12-MBA-DNA adducts eluted. A major DMBA-DNA adduct formed in this in vitro system eluted with the same retention time as did the major 7-OHM-12-MBA-DNA adduct formed in mouse skin in vivo. These results when coupled with the in vivo data suggest that 7-OHM-12-MBA is an intermediate for at least some of the binding of DMBA to epidermal DNA in Sencar mice.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives / Q000378:metabolism*; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D005260:Female; D051379:Mice; D008815:Mice, Inbred Strains; D012867:Skin / Q000378:metabolism*; D014316:Tritium
D001551:Benz(a)Anthracenes; D014316:Tritium; C018970:7-hydroxymethyl-12-methylbenz(a)anthracene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA