Bioalkylation of dibenz[a,b]anthracene in rat liver cytosol.
Previous studies by other investigators have established that L-region methyl derivatives of dibenz[a,h]anthracene (DBA) were more carcinogenic than the parent hydrocarbon. The bioalkylation of DBA was investigated by incubating the hydrocarbon with rat liver cytosol fortified with S-adenosyl-L-methionine (SAM) in 0.1 M phosphate buffer (pH 7.4) for 1 h at 37 degrees C in air. The reaction was stopped by the addition of cold acetone and the mixture extracted with ethyl acetate and washed with water. The organic phase was evaporated and the residue dissolved in methylene chloride for analysis by reverse phase high performance liquid chromatography (HPLC) and gas chromatography/mass spectroscopy GC/MS. Products were found that were indistinguishable from 7-methyl-DBA and 7,14-dimethyl-DBA, 7-hydroxymethyl-DBA, 7-hydroxymethyl-14-methyl-DBA, and 7,14-dihydroxymethyl-DBA. The results suggest that unsubstituted carcinogenic hydrocarbons are preprocarcinogens that react with SAM in liver cytosol preparations, to form alkyl substituted procarcinogens, which are more potent than the corresponding preprocarcinogens.
D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol; D008401:Gas Chromatography-Mass Spectrometry; D008099:Liver / Q000378:metabolism*; D008297:Male; D008745:Methylation; D010084:Oxidation-Reduction; D051381:Rats; D012436:S-Adenosylmethionine / Q000378:metabolism
D001551:Benz(a)Anthracenes; D012436:S-Adenosylmethionine; C026486:1,2,5,6-dibenzanthracene