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 on the quantification of bleomycin (BLM)-induced chromatid breaks in short-term cultured peripheral lymphocytes, can be a marker of cancer susceptibility. Although many factors can contribute to variability in human biomonitoring studies, genetic susceptibility (the influence of polymorphic metabolising genes on response to environmental mutagens) should be considered whenever appropriate. Glutathione-S-transferases (GSTs) encode a family of detoxifying phase II enzymes catalysing the conjugation of glutathione to electrophilic compounds. Studies on Caucasians indicate that about 45% of individuals lack the glutathione-S-transferase M1 (GSTM1, null) enzyme, and are therefore, 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 [corrected] level of DNA 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 cytogenetic techniques were used in mitogen-stimulated lymphocytes treated with BLM. Without BLM treatment, individuals with the GSTM1 null genotype had no significant difference in frequencies of damaged cells by comparison to individuals 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.
Kocabaş
N A
NA
Department of Toxicology, Faculty of Pharmacy, Gazi University, Hipodrom, 06330, Ankara, Turkey.
Karahalil
B
B
Karakaya
A E
AE
Sardaş
S
S
D000328:Adult; D001483:Base Sequence; D001761:Bleomycin / Q000633:toxicity*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D020552:Comet Assay; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000201:enzymology / Q000209:etiology / Q000235:genetics; D012307:Risk Factors
D001761:Bleomycin; D017931:DNA Primers; D005982:Glutathione Transferase