Mutagenicity of epoxides of polycyclic hydrocarbons correlates with carcinogenicity of parent hydrocarbons.

Abstract

MANY chemical carcinogens are mutagenic1 and some non-mutagenic carcinogens are metabolized to mutagenic derivatives2,3. Recent work4–6 has confirmed that epoxides are intermediates in the metabolism of the aromatic double bonds of carcinogenic polycyclic hydrocarbons to hydroxylated derivatives, as Boyland suggested7. In addition to chemical reactions with nucleic acids and histone8, epoxides derived from polycyclic hydrocarbons bind more extensively to the nucleic acids of cells in culture than the parent hydrocarbons9. Hydrocarbon epoxides are also more active in inducing malignant transformation in vitro of hamster embryo and mouse prostate cells10 although, in whole animals, they were less potent carcinogens than the hydrocarbons themselves11–13. As potential mutagens, polycyclic hydrocarbon epoxides are therefore of particular interest, mainly because of the support positive results would give to the somatic mutation theory of carcinogenesis. In the work described here we have tested K-region epoxides of hydrocarbons for their ability to cause host range mutations of T2h+ bacteriophage, specifically because there is no possibility, in this test system, of the epoxides being further metabolized. The epoxides tested were phenanthrene 9,10-oxide (Ph-E), benz(a)anthracene 5,6-oxide (BA-E), dibenz(a,h)anthracene 5,6-oxide (DBA-E), 7-methylbenz(a)anthracene 5,6-oxide (7-MeBA-E), 3-methylcholanthrene 11,12-oxide (MCA-E) and chrysene 5,6-oxide (Ch-E). Ethylene oxide and propylene oxide were used as examples of aliphatic epoxides which do not increase the frequency of host range mutants of T2 bacteriophage and ethyl methanesulphonate (EMS) was used as a known mutagen14.