Increased cytogenetic damage in smokers deficient in glutathione S-transferase isozyme mu.
Reduced expression of the mu-isozyme of glutathione S-transferase (GST; EC 2.5.1.18) has been associated with increased lung cancer risk. We studied the association between GST-mu expression and DNA damage as measured by sister chromatid exchanges (SCE) in healthy male smokers. SCE levels were higher in the 71 GST-mu-deficient smokers compared to the 83 non-deficient smokers (5.24 versus 4.97 SCE/lymphocyte; P = 0.09). In smokers having high plasma cotinine levels (greater than median of 315 ng/ml), this mu-related difference was more pronounced (5.50 versus 4.97; P = 0.01), whereas it was absent in smokers having low cotinine levels (4.95 versus 4.97; P = 0.92). Increased cytogenetic damage in GST-mu-deficient heavy smokers may thus explain the association between GST-mu expression and lung cancer.
van Poppel
G
G
TNO Toxicology and Nutrition Institute, Zeist, The Netherlands.
de Vogel
N
N
van Balderen
P J
PJ
Kok
F J
FJ
D000328:Adult; D002849:Chromatography, Gas; D004249:DNA Damage; D004797:Enzyme-Linked Immunosorbent Assay; D005982:Glutathione Transferase / Q000172:deficiency*; D006801:Humans; D007527:Isoenzymes / Q000172:deficiency; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000097:blood; D012854:Sister Chromatid Exchange; D012907:Smoking / Q000378:metabolism*
D007527:Isoenzymes; D009538:Nicotine; D005982:Glutathione Transferase