Mutagenicity of hexahydrophenanthrenes and their oxirane derivatives.
The mutagenicity of some hexahydrophenanthrenes and their corresponding arene oxides was assayed in histidine-dependent mutants of Salmonella typhimurium TA98 and TA100. All the arene epoxides examined were devoid of mutagenic activity, although some of them could alkylate nicotinamide. By contrast, the 1,2,3,9,10, 10a-hexahydrophenanthrene, trans-1,2,3,4,4a,10a-hexahydrophenanthrene, 9-methyl-, 6-methoxy-trans-1,2,3,4,4a,10a-hexahydrophenanthrene, 7-bromo-trans-1,2,3,4,4a,10a-hexahydrophenanthrene and 9-methyl-trans-1,2,3,4,4a,10a-hexahydrophenanthrene were active as mutagens in the presence of S9 mix. A negative result was obtained with octahydrophenanthrene, suggesting that the benzylic double bond is a prerequisite for the mutagenic activities of hexahydrophenanthrenes. Thus, probably a very reactive intermediate (aryloxirane) formed by a secondary metabolism following the primary oxidation of the benzylic double bond by S9 mix could be responsible for the mutagenicity of the hexahydrophenanthrenes.
Crotti
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Dipartimento di Chimica Bioorganica, Facoltà di Farmacia, Pisa, Italy.
Di Bussolo
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V
Benetti
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D
Longo
V
V
Gervasi
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PG
D004852:Epoxy Compounds / Q000378:metabolism / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D010616:Phenanthrenes / Q000378:metabolism / Q000633:toxicity*; D012486:Salmonella typhimurium
D004852:Epoxy Compounds; D009153:Mutagens; D010616:Phenanthrenes