This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fahmy, O. G. Articles by Fahmy, M. J. Search for Related Content PubMed PubMed Citation Articles by Fahmy, O. G. Articles by Fahmy, M. J.

Oxidative Activation of Benz[a]anthracene and Methylated Derivatives in Mutagenesis and Carcinogenesis¹

Department of Genetics, Institute of Cancer Research, Chester Beatty Research Institute, Royal Cancer Hospital, Fulham Road, London SW3 6JB, England

Comparative genetic studies in Drosophila with benz[a]anthracene, its 7-methyl and 7,12-dimethyl substituents, 3-methylcholanthrene, and their epoxides revealed that K-region oxidation dramatically altered the mutational spectrum of the hydrocarbon. The parent compounds were virtually inactive on the euchromatic parts of the genome but were effective on certain heterochromatic sites, especially the rRNA genes that yield bobbed mutations. This specific mutability was substantially higher for the methylated derivatives but did not appear to be dose dependent. In contrast, the K-region epoxides were decisively mutagenic on the euchromatic genes and were less effective on the rRNA loci than the corresponding parent hydrocarbons, and their mutagenicity was dose dependent.

Mutagenic selectivity for the rRNA genes was quantitatively measured in terms of an index which was defined as the percentage proportion of bobbed mutants relative to the total X chromosome mutations recovered from the same sample of treated gametes. Statistical studies revealed that the genetic selectivity indices for a series of structurally related benz[a]anthracenes showed a highly significant correlation to their relative carcinogenic potencies in rodent skin, both at the rank level and when expressed as Iball's indices. The genetic and oncogenic indices for the K-region epoxides were invariably lower than those for the corresponding parent hydrocarbons, which argued against the suggestion that such oxidative products could be regarded as the ultimate carcinogens.

¹ This work was supported by grants to the Chester Beatty Research Institute (Institute of Cancer Research, Royal Cancer Hospital) from the Medical Research Council and the Cancer Research Campaign.

Received 4/ 9/73. Accepted 6/11/73.

This article has been cited by other articles:

				D. M. Jerina and J. W. Daly Arene Oxides: A New Aspect of Drug Metabolism Science, August 16, 1974; 185(4151): 573 - 582. [PDF]