The influence of GSTM1 null genotype on susceptibility to in vitro oxidative stress

From epidemiological studies, there is some evidence that genetic variation at the glutathione S-transferase (CST) loci GSTM1 influences individual su sceptibility to disease associated with oxidative stress. The aim of this s tudy was to elucidate the role of the GSTM1 genotype in protection against oxidant chemicals by comparing the sensitivity, genotoxicity and cytotoxici ty of lymphocytes to benzo(a)pyrene (BaP)- and cumene hydroperoxide (CumOOH )-induced in vitro oxidative challenge. Malondialdehyde and protein carbony l levels, and oxidation of 2',7'-dichlorofluorescin diacetate were used as biomarkers of oxidative stress in lymphocytes. Following supplementation wi th BaP or CumOOH, time-dependent increases were observed in the production of all the markers after incubation for 12-48 h. However, we could not find any differences between GSTM1 null and positive genotypes. Furthermore, do se or time response experiments indicated that GSTM1-deficient cells were n ot more sensitive than control cells to BaP-or CumOOH-induced cell killing and micronucleus formation, although they were hypersensitive to BaP-inhibi ted cellular growth. The results suggest that lymphocytes from individuals with the GSTM1 null genotype are not abnormally susceptible to in vitro ind uced oxidant challenge, when exposed to CumOOH. (C) 2001 Elsevier Science I reland Ltd. All rights reserved.