title: Reactions of the carcinogens 7-hydroxymethyl-12-methylbenz(A)anthracene and 7-acetoxymethyl-12-methylbenz(A)anthracene with DNA.
abstract: The carcinogen 7-hydroxymethyl-12-methylbenz(a)anthracene reacts very poorly with DNA (2 mumoles hydrocarbon/mole DNA P) in the absence of enzymes whereas the carcinogen 7-acetoxymethyl-12-methylbenz(a)-anthracene reacts readily with DNA (21.4 mumoles hydrocarbon/mole DNA DNA P). The high reactivity of the acetoxymethyl compound suggests it functions as an ultimate carcinogen whereas the low reactivity of the hydroxymethyl compound suggests that it requires further mebabolism to a reactive ester (e.g. sulfate) before it becomes an ultimate carcinogen. To test this hypothesis tritium labeled 7-hydroxymethyl-12-methylbenz(a)anthracene was synthesized and reaction with calf thymus DNA studied in the presence and absence of a PAPS generating system. The results demonstrate that in the absence of a PAPS generating system and ATP, virtually no reaction with DNA could be detected. However, in the presence of the complete system, the radioactivity associated with phenol-extracted ethanol precipitated DNA was 27.5 mumoles of hydrocarbon/mole DNA P. The reaction with DNA was shown to be only partially dependent on sulfate ion which when omitted from the reaction mixture gave 22.7 mumoles of hydrocarbon/mole DNA P, whereas if ATP were omitted, no reaction occurred (0.4 mumoles/mole DNA P). However, if enzyme is omitted from the system, reaction occurs in the presence (44.8 mumoles/mole DNA P), but not in the absence of ATP. These data demonstrate that ATP mediates the reaction of this hydrocarbon with DNA, suggesting the formation of a reactive phosphate ester.
mesh_terms: D000227:Adenine Nucleotides / Q000494:pharmacology; D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D001711:Biotransformation; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats
chemical_list: D000227:Adenine Nucleotides; D001551:Benz(a)Anthracenes; D004247:DNA