title: Effects of cigarette smoking and exposure to cadmium and lead on phenotypic variability of hepatic CYP2A6 and renal function biomarkers in men.
abstract: Effects of cigarette smoking and exposure to dietary cadmium (Cd) and lead (Pb) on urinary biomarkers of renal function and phenotypic variability of cytochrome P450 2A6 (CYP2A6) were investigated in a group of 96 healthy Thai men with mean age of 36.7 year (19-57 years). In non-smokers, Cd burden increased with age (r = 0.47, P < 0.001). In current smokers, Cd burden increased with both age (r = 0.45, P = 0.01) and number of cigarettes smoked per day (r = 0.32, P = 0.05). Cd-linked renal tubular dysfunction was seen in both smokers and non-smokers, but Pb-linked glomerular dysfunction was seen in smokers only, possibly due to more recent exposure to high levels of Cd and Pb, as reflected by 30-50% higher serum Cd and Pb levels in smokers than non-smokers (P < 0.05). Exposure to dietary Cd and Pb appeared to be associated with mild tubular dysfunction whereas dietary exposure plus cigarette smoking was associated with tubular plus glomerular dysfunction. Hepatic CYP2A6 activity in non-smokers showed a positive association with Cd burden (adjusted beta = 0.38, P = 0.006), but it showed an inverse correlation with Pb (adjusted beta = -0.29, P = 0.003), suggesting opposing effects of Cd and Pb on hepatic CYP2A6 phenotype. In contrast, CYP2A6 activity in current smokers did not correlate with Cd or Pb, but it showed a positive correlation with serum ferritin levels (r = 0.45, P = 0.01). These finding suggest that Pb concentrations in the liver probably were too low to inhibit hepatic synthesis of heme and CYP2A6 and that the concurrent induction of hepatic CYP2A6 and ferritin was probably due to cigarette smoke constituents other than Cd and Pb.
authors.affiliation: National Research Centre for Environmental Toxicology (EnTox), The University of Queensland, 39 Kessels Road, Coopers Plains, Brisbane, Qld 4108, Australia. s.satarug@uq.edu.au
authors.forename: Soisungwan
authors.initials: S
authors.lastname: Satarug
authors.forename: Pailin
authors.initials: P
authors.lastname: Ujjin
authors.forename: Yuvaree
authors.initials: Y
authors.lastname: Vanavanitkun
authors.forename: Muneko
authors.initials: M
authors.lastname: Nishijo
authors.forename: Jason R
authors.initials: JR
authors.lastname: Baker
authors.forename: Michael R
authors.initials: MR
authors.lastname: Moore
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D015415:Biomarkers / Q000652:urine; D002104:Cadmium / Q000494:pharmacology* / Q000652:urine; D065637:Cytochrome P-450 CYP2A6; D014644:Genetic Variation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D007854:Lead / Q000494:pharmacology* / Q000652:urine; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010641:Phenotype; D012907:Smoking / Q000235:genetics* / Q000378:metabolism; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers; D002104:Cadmium; D007854:Lead; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6