Sex differences in lung CYP1A1 expression and DNA adduct levels among lung cancer patients.
Several epidemiological studies have indicated that female tobacco smokers may be at higher risk of lung cancer than males. In a study of lung cancer cases, we have found that female smokers had a significantly higher level of aromatic/hydrophobic DNA adducts in their nontumor lung tissue (15.39+/-9.47 adducts/10(8) nucleotides, n = 29) than male smokers (12.08+/-8.14, a = 93; P = 0.047). Females had significantly higher levels of adducts/pack-year (females 0.95+/-0.82 adducts/pack-year and males 0.46+/-0.46; P = 0.0004) and adducts/cigaret/day (females 1.48+/-1.29 and males 0.89+/-0.74, P = 0.015). By quantitative reverse transcription-PCR, it was found that female smokers exhibited a significantly higher expression level of lung CYP1A1 (494+/-334 CYP1A1 mRNA/10(6) glyceraldehyde-3-phophate dehydrogenase mRNA, n = 15) compared with males (210+/-208, n = 12; P = 0.016). Furthermore, for both sexes combined a significant correlation between CYP1A1 expression and DNA adduct level was found (r = 0.50, P = 0.009). In conclusion, the observed sex difference in aromatic/hydrophobic DNA adduct levels may at least in part be explained by different levels of CYP1A1 expression.
Mollerup
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S
Department of Toxicology, National Institute of Occupational Health, Oslo, Norway. Steen.Mollerup@stami.no
Ryberg
D
D
Hewer
A
A
Phillips
D H
DH
Haugen
A
A
D000328:Adult; D000368:Aged; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000187:drug effects; D018736:DNA Adducts / Q000032:analysis*; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000235:genetics; D004790:Enzyme Induction; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009603:Nitroso Compounds / Q000009:adverse effects / Q000494:pharmacology; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects
D018736:DNA Adducts; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009603:Nitroso Compounds; D011084:Polycyclic Aromatic Hydrocarbons; D004247:DNA; D019363:Cytochrome P-450 CYP1A1