Evidence for concurrent effects of exposure to environmental cadmium and lead on hepatic CYP2A6 phenotype and renal function biomarkers in nonsmokers.
We examined the interrelationships between phenotype of hepatic cytochrome P450 2A6 (CYP2A6), nephropathy, and exposure to cadmium and lead in a group of 118 healthy Thai men and women who had never smoked. Their urinary Cd excretion ranged from 0.05 to 2.36 microg/g creatinine, whereas their urinary Pb excretion ranged from 0.1 to 12 microg/g creatinine. Average age and Cd burden of women and men did not differ. Women, however, on average showed a 46% higher urinary Pb excretion (p < 0.001) and lower zinc status, suggested by lower average serum Zn and urinary Zn excretion compared with those in men. Cd-linked nephropathy was detected in both men and women. However, Pb-linked nephropathy was seen only in women, possibly because of higher Pb burden coupled with lower protective factors, notably of Zn (p < 0.001), in women compared with men. In men, Pb burden showed a negative association with CYP2A6 activity (adjusted beta = -0.29, p = 0.003), whereas Cd burden showed a positive association with CYP2A6 activity (adjusted beta = 0.38, p = 0.001), suggesting opposing effects of Cd and Pb on hepatic CYP2A6 phenotype. The weaker correlation between Cd burden CYP2A6 activity in women despite similarity in Cd burden between men and women is consistent with opposing effects of Pb and Cd on hepatic CYP2A6 phenotypic expression. A positive correlation between Cd-linked nephropathy (urinary N-acetyl-beta-D-glucosaminidase excretion) and CYP2A6 activity in men (r = 0.39, p = 0.002) and women (r = 0.37, p = 0.001) suggests that Cd induction of hepatic CYP2A6 expression and Cd-linked nephropathy occurred simultaneously.
Satarug
Soisungwan
S
National Research Centre for Environmental Toxicology, University of Queensland, Brisbane, Australia. s.satarug@uq.edu.au
Nishijo
Muneko
M
Ujjin
Pailin
P
Vanavanitkun
Yuvaree
Y
Baker
Jason R
JR
Moore
Michael R
MR
D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis; D002104:Cadmium / Q000493:pharmacokinetics*; D002105:Cadmium Poisoning / Q000503:physiopathology*; D065637:Cytochrome P-450 CYP2A6; D004032:Diet; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D007854:Lead / Q000493:pharmacokinetics*; D007855:Lead Poisoning / Q000503:physiopathology*; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000494:pharmacology*; D010641:Phenotype; D012737:Sex Factors; D014018:Tissue Distribution; D015032:Zinc / Q000032:analysis
D015415:Biomarkers; D002104:Cadmium; D007854:Lead; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D015032:Zinc