Mutagenicity in Salmonella and sister chromatid exchange in mice for the bay-region syn- and anti-diol epoxides of 1,4-dimethylphenanthrene.
Dose-response relationships for (+/-)-7 alpha,8 beta-dihydroxy-5 beta,6 beta-epoxy-1,4-dimethyl-5,6,7,8-tetrahydrophenanthrene and its 5 alpha,6 alpha-epoxy diastereomer, the syn- and anti-diol epoxides of 1,4-dimethylphenanthrene respectively, have been established for their mutagenicity in Salmonella strains TA98 and TA100 and for their in vivo sister chromatid exchange in the bone-marrow cells of mice. Both isomers were mutagenic in the eta mole per plate range with the syn isomer being in the order of fifteen times more active with TA98 and five times more mutagenic in TA100 than its anti isomer. The anti isomer was more genotoxic in the sister chromatid exchange assay than the syn isomer. Statistically significant results were obtained as low as 1.5 mg/kg body weight for the anti isomer and 3 mg/kg for the syn isomer. The present study supports the inclusion of methyl-substituted bay-region diol epoxides in the concept that the syn isomer, with quasi-diequatorial hydroxyl groups, can contribute to the genotoxicity of the parent polycyclic aromatic hydrocarbons of those compounds which form hindered bay-region diol epoxides.
Sinsheimer
J E
JE
College of Pharmacy, University of Michigan, Ann Arbor 48109.
Giri
A K
AK
Messerly
E A
EA
Jung
K Y
KY
Koreeda
M
M
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D008297:Male; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D010616:Phenanthrenes / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013329:Structure-Activity Relationship
D009153:Mutagens; D010616:Phenanthrenes; C059986:7,8-dihydroxy-5,6-epoxy-1,4-dimethyl-5,6,7,8-tetrahydrophenanthrene