GSTM1, GSTT1, and GSTP1 polymorphism in north Indian population and its influence on the hydroquinone-induced in vitro genotoxicity.
Glutathione S transferase (GST) gene polymorphism examined among north Indians and correlated with hydroquinone (HQ) genotoxicity to help in clinical prediction of susceptibility of HQ toxicity. Lymphocytes of individuals with/without GSTM1, GSTT1, and GSTP1 (ile/ile or val/val) were exposed to HQ (20, 40, or 80 microM) and examined chromosomal aberrations (CA) or cytokinesis-block micronucleus assays. Among north Indians the frequencies of GSTM1 (null), GSTT1 (null), and both null were found to be 41.1, 21.9, and 12.7%, whereas frequencies of GSTP1 with (ile/ile) or (ile/val), or (val/val) were 52, 42.1, or 5.9%, respectively. Individuals with null GSTM1, GSTT1, and GSTP1 (val/val) showed inhibition of mitotic index (MI) and significant (p < 0.01) induction of CA as compared to individuals with GSTM1, GSTT1, and GSTP1 (ile/ile). Micronucleus formation was found to be significant (p < 0.05 or 0.01) in both the genotypes. Results indicate that GSTM1, GSTT1 (null), and GSTP1 (val/val) are sensitive to HQ genotoxicity.
Petroleum Toxicology Division, Indian Institute of Toxicology Research, Lucknow-226001, India.
Munish
M
Kumar
L K S
LK
Chauhan
B N
BN
Paul
Sudhir K
SK
Agarwal
Sudhir K
SK
Goel
D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D007194:India; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D008875:Middle Aged; D008940:Mitotic Index; D009153:Mutagens / Q000633:toxicity*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D055815:Young Adult
D004247:DNA; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D006873:Hydroquinones; D009153:Mutagens; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; C031927:hydroquinone