REACTIONS OF CARCINOGENS 7-HYDROXYMETHYL-12-METHYLBENZ (A) ANTHRACENE AND 7-ACETOXYMETHYL-12-METHYLBENZ (A) ANTHRACENE WITH DNA

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 22  (2) , 345-355
Abstract
The carcinogen 7-hydroxymethyl-12-methylbenz(a)anthracene reacts very poorly with DNA (2 .mu.mol hydrocarbon/mol DNA P [phosphate]) in the absence of enzymes whereas the carcinogen 7-acetoxymethyl-12-methylbenz(a)-anthracene reacts readily with DNA (21.4 .mu.mol hydrocarbon/mol 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 metabolism to a reactive ester (e.g., sulfate) before it becomes an ultimate carcinogen. 3H- 7-hydroxymethyl-12-methylbenz(a)anthracene was synthesized and reaction with calf thymus DNA studied in the presence and absence of a PAPS [3''-phosphoadenosine-5''-phosphosulfate] generating system. In the absence of a PAPS generating system and ATP virtually no reaction with DNA could be detected. In the presence of the complete system the radioactivity associated with phenol-extracted ethanol precipitated DNA was 27.5 .mu.mol of hydrocarbon/mol DNA P. The reaction with DNA was only partially dependent on sulfate ion which when omitted from the reaction mixture gave 22.7 .mu.mol of hydrocarbon/mol DNA P whereas if ATP were omitted, no reaction occurred (0.4 .mu.mol/mol DNA P). If enzyme is omitted from the system, reaction occurs in the presence (44.8 .mu.mol/mol DNA P) but not in the absence of ATP. ATP apparently mediates the reaction of this hydrocarbon with DNA, suggesting the formation of a reactive phosphate ester.

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