Human Glutathione 5-Transferase Deficiency as a Marker of Susceptibility to Epoxide-induced Cytogenetic Damage

John K. Wiencke, Karl T. Kelsey, Rosito A. Lamela, William A. Toscano

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129 Scopus citations


The identification of genetic traits that predispose individuals to environmentally induced cancers is one of the most important problems in cancer risk assessment. Genetic deficiency in the µ-isozyme of the glutathione (GSH) 5-transferases (EC has recently been associated with increased lung cancer risk. To test whether this association could arise from a metabolically mediated sensitivity to mutagenic substrates, cytogenetic damage in lymphocytes from 21 isozyme-deficient and 24 nondeficient individuals was induced. Cells were treated with trans-stilbene oxide, an excellent substrate for GSH S-transferase μ, or cis-stilbene oxide, a poor substrate for the isozyme. Sister chromatid exchange induction was measured as an indicator of cytogenetic damage. A trimodal distribution of trans-stilbene oxide-induced sister chromatid exchanges was observed in the population, including resistant, moderate, and highly sensitive groups. Glutathione S-transferase μ deficiency was associated with both moderate and high sensitivity to fnms-stilbene oxide-induced damage but had no effect on cis-stilbene oxide-induced sister chromatid exchange. The results indicate that GSH 5-transferase μ a proposed marker of cancer susceptibility, is also a marker of susceptibility to the induction of cytogenetic damage by a certain class of mutagens. The differential effects of the cis- and trans-isomers of stilbene oxide illustrate that the stereoselectivity of GSH 5-transferase μ toward various alkene epoxide substrates can be an important factor affecting individual sensitivity to DNA-damaging epoxides.

Original languageEnglish (US)
Pages (from-to)1585-1590
Number of pages6
JournalCancer Research
Issue number5
StatePublished - Mar 1 1990


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