Comparison of the mutagenicity of aristolochic acid I and aristolochic acid II in the gpt delta transgenic mouse kidney

Abstract Aristolochic acid (AA) is known to be a potent mutagen and carcinogen. Aristolochic acid I (AAI) and aristolochic acid II (AAII), the two major components of AA, differ from each other by a single methoxy group. However, their individual mutagenic characteristics in vivo are unclear. In the present study, we compared their DNA adduct formation and mutagenicities in the gpt delta transgenic mouse kidney. The dA-AAI, dG-AAI, dA-AAII and dG-AAII were identified in the kidney two days after intragastric administration of AAI or AAII at 5 mg/kg. The concentration of DNA adducts formed by AAII was approximately 2.5-fold higher than that formed by AAI ( p p p  > 0.05). A:T to T:A transversion was the predominant type of mutation in both treated groups, the GC-associated mutation rates, however, differed between the AAI and AAII treatments. The in vivo metabolic pathways of AAI and AAII are different, and this may affect their mutagenicity. In the present study, we measured the levels of AAI and AAII in the kidney and plasma of gpt delta transgenic mice at multiple time points after a single intragastric dose of 1 or 5 mg/kg of either component. Our results showed that the levels of AAII in both kidney and plasma were considerably higher than those of AAI ( p in vivo , and this may be, at least partly, the result of its increased levels in kidney and plasma.