Upregulation of gamma-glutamyl-transpeptidase activity and uric acid level in mixed chemical exposure: implications for mutagenic and preneoplastic events

Abstract

Mixed chemical toxicity including genotoxicity is currently a major concern in rapidly industrializing developing countries. Simple biomarkers remain a constraint. Gamma-glutamyl-transpeptidase (GGT), a precursor of glutathione, protects against chemical toxicity including genotoxic effects and may serve as a marker for pre-neoplastic lesion. The objective of the study was to determine a possible relationship between GGT, uric acid and the angiogenic agent copper (Cu) in mixed chemical exposure. Sixty-six individuals occupationally exposed to mixed chemicals, mean age 34.4 ± 1.27 years, classified into 3 groups based on duration of exposure as follows: 1-10, 11-20 and > 20 years respectively, were enrolled into the study. Twentyseven, age- and sex-matched apparently healthy, occupationally unexposed individuals served as controls. The results showed that serum GGT was higher but not significantly different in exposed participants compared with controls; while its levels varied significantly with duration of exposure across the exposure groups. Like GGT, uric acid was significantly higher in the exposed than in controls and both significantly positively correlated with duration of exposure. Copper was higher in the exposed than the unexposed controls and correlated positively with GGT but not significantly. This observed up-regulation of GGT and its positive correlation with uric acid levels may be a protective response against oxidative stress arising from or related to the depletion of thiol group; thus enhancing maintenance of GSH levels; and may serve as an inexpensive early biomarker of mutagenicity in mixed chemical exposure.

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Keywords: Gamma-glutamyl-transpeptidase, uric acid, mixed chemical exposure, genotoxicity, mutagenicity