Inhibitory Effect of Vitamin C on Mutagenicity of 6-Sulfooxymethylbenzo[a]pyrene

  • Published : 1996.06.01

Abstract

Vitamin C has been well known to be a potential chemopreventive agent for several toxic compounds. It reduced the mutation frequencies of 6-sulfooxymethylbenzo[a]pyrene (SMBP) and 6hydroxymethylbenzo[a]pyrene (HMBP) in Salmonella typhimurium TA98 and TA100, indicating that corbic acid affects both frameshift and base-pair substitution mtltations. A similar type of dose-response relationship was shown in the V79 cells, although the inhibitory effect was less dramatic compared with that in S. typhimurium. However, SMBP or HMBP binding to calf thymus DNA was not affected by the presence of vitamin C, suggesting that SMBP seems to be much more reactive to calf thymus DNA than vitamin C. This was supported by migration pattern and fluorescence intensity of SMBP-modified plasmid on the gel. These restilts were not correlated with mutation tests in bacterial and mammalian cell systems. It has been already reported that vitamin C inactivates SMBP through the formation of covalently bound addact. It was found from HPLC analysis that the reaction between vitamin C and SMBP was accomplished within just 5 min and then produced the several products. These findings indicate that the beneficiary of vitamin C is not merely derived from the covalent adducts. On the other hand, the addition of DNA to incubation mixture reduced the amounts of vitamin C adducts while the magnitude of HMBP peak increased, suggesting that DNA accelerates the SMBP hydrolysis to intercept the interaction between SMBP and vitamin C or forms rapidly complex with SMBP.

Keywords

References

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