Influence of GSTM1 genotype on comet assay and chromosome aberrations after induction by bleomycin in cultured human lymphocytes

Investigators have demonstrated that the mutagen sensitivity assay, based o n the quantification of bleomycin (BLM)-induced chromatid breaks in short-t erm cultured peripheral lymphocytes, can be a marker of cancer susceptibili ty. Although many factors can contribute to variability in human biomonitor ing studies, genetic susceptibility (the influence of polymorphic metabolis ing genes on response to environmental mutagens) should be considered whene ver appropriate. Glutathione-S-transferases (GSTs) encode a family of detox ifying phase II enzymes catalysing the conjugation of glutathione to electr ophilic compounds. Studies on Caucasians indicate that about 45% of individ uals lack the glutathione-S-transferase M1 (GSTM1, null) enzyme, and are th erefore, theoretically at a higher risk to the toxic effects of chemicals. The aim of the present study was to investigate this hypothesis further by evaluating whether the GSTM1 genotype influences the background level of DN A damage and the induction of chromosomal aberrations by BLM in peripheral- blood lymphocytes. The alkaline comet assay was used to evaluate background levels of DNA damage in unstimulated lymphocytes while standard cytogeneti c techniques were used in mitogen-stimulated lymphocytes treated with BLM. Without BLM treatment, individuals with the GSTM1 null genotype had no sign ificant difference in frequencies of damaged cells by comparison to individ uals with the GSTM1 genotype. Also, no significant differences between the two groups of individuals (GSTM1 positive and GSTM1 null) were observed for BLM-induced chromosomal aberrations. (C) 2000 Elsevier Science B.V. All ri ghts reserved.