The envieonmental pollutant 6-nitrochrysene (6-NC), a powerful mammary carcinogen in rats,   produces several DNA adducts with the major one derived from the metabolite (�)-trans-1,2-dihydroxy-1,2-dihydro-6-nitrochrysene (1,2-DHD-6-NC) which is resolved to (-)-[R,R]- and (+)-[S,S] -1,2-DHD-6-NC.  Here, we compared the mutagenicity and carcinogenicity of the two enantiomers in the rat mammary gland using female transgenic (BigBlue F344 � Sprague-Dawley)F1 rats harboring lacI/cII gene and female Sprague-Dawley rats, respectively; 6-NC was used as a positive control.  Unlike other optical isomers of dihydrodiol metabolites derived from bulky aromatic compunds, the two enantiomers exerted similar activity but weaker than 6-NC.  Using immunoblot analysis, these compounds similarly induced stress related proteins (p53, p38 and JNK) in breast cancer MCF-7 cells.  Taken together, our results suggest that genotoxic mechanisms may not fully account for the potent mammary carcinogenicity of 6-NC.

Comparable mutagenicity and carcinogenicity of <i>(-)-[R,R]</i>- and <i>(+)-[S,S]-trans</i>-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene in the rat mammary gland

244th National Meeting (2012)

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Comparable mutagenicity and carcinogenicity of (-)-[R,R]- and (+)-[S,S]-trans-1,2-dihydro-1,2-dihydroxy-6-nitrochrysene in the rat mammary gland