Abstract

This cytogenetic and pharmacological study attempts to clarify genotoxicity-enhancement-effect of dl-α-tocopherol (one form of vitamin E) in combination with the herbicide 1,1'-dimetyl-4,4'-bipyridium dichloride (paraquat, PQ) on cultured anuran leukocytes using the superoxide dismutase-mimic Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (Mn(III)TMpyP), the hydrogen peroxide-scavenger catalase and the electron donor nicotinamide adenine dinucleotido phosphate (NADPH). PQ only was found to induce structural chromosomal damage in cultured anuran leukocytes in a dose-dependent manner. PQ plus NADPH, which served as positive control, enhanced the genotoxic effect of PQ. Dl-α-tocopherol only did not induce any structural chromosomal damage in the leukocytes. PQ plus dl-α-tocopherol, however, enhanced the genotoxic effect of PQ. PQ plus Mn(III)TMpyP, PQ plus catalase and PQ plus Mn(III)TMpyP plus catalse suppressed the genotoxic effect of PQ. Furthermore, PQ plus dl-α-tocopherol-enhanced chromosomal damage was also inhibited by Mn(III)TMpyP plus catalase. These results suggest that dl-α-tocopherol in combination with PQ functions as an electron donor to PQ.

Highlights

  • This cytogenetic and pharmacological study attempts to clarify genotoxicity-enhancement-effect of dl-α-tocopherol in combination with the herbicide 1,1’-dimetyl-4,4’-bipyridium dichloride on cultured anuran leukocytes using the superoxide dismutase-mimic Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (Mn(III)TMpyP), the hydrogen peroxidescavenger catalase and the electron donor nicotinamide adenine dinucleotido phosphate (NADPH)

  • I failed to find the fragile sites of damaged chromosomes no. 1 and no. 2 in group 6 leukocytes, but chromosomal breaks occurred in short arm of no. 1 chromosome in the same group leukocytes are likely to be caused more than the others

  • The results show that PQ induces structural chromosomal damage

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Summary

Introduction

This cytogenetic and pharmacological study attempts to clarify genotoxicity-enhancement-effect of dl-α-tocopherol (one form of vitamin E) in combination with the herbicide 1,1’-dimetyl-4,4’-bipyridium dichloride (paraquat, PQ) on cultured anuran leukocytes using the superoxide dismutase-mimic Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (Mn(III)TMpyP), the hydrogen peroxidescavenger catalase and the electron donor nicotinamide adenine dinucleotido phosphate (NADPH). PQ plus dl-α-tocopherol-enhanced chromosomal damage was inhibited by Mn(III)TMpyP plus catalase These results suggest that dl-α-tocopherol in combination with PQ functions as an electron donor to PQ. Dl-α-tocopherol (α-TH) antioxidant-defense-system functions in inhibiting unsaturated fatty acids (UFAs) autoxidation that is a free radical chain reaction Functional disruption in this defense system promotes accumulation of reactive oxygen species (ROS) involved in induction of chromosomal damage. Mn(III)TMpyP has dismutation-reaction property that is conversion of superoxide (O2Ϫ) into hydrogen peroxide (H2O2) (PASTERNACK et al 1981) This substance has suppressive effect on ischemia/ reperfusion-induced O2Ϫ generation leading to rat renal DNA damage (LIANG et al 2009).

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