Relationships between non-occupational cadmium exposure and expression of nine cytochrome P450 forms in human liver and kidney cortex samples

Jason R. Baker, Soisungwan Satarug, Paul E B Reilly, Robert J. Edwards, Noritaka Ariyoshi, Tetsuya Kamataki, Michael R. Moore, David J. Williams

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Abstract

This study was undertaken to assess associations between age, gender, cigarette smoke and non-workplace cadmium exposure, and liver pathology and inter-individual variation in cytochrome P450 (CYP) expression in human tissues. Autopsy specimens of twenty-eight Queensland residents whose ages ranged from 3 to 89 years were analyzed for the presence of nine CYP protein isoforms by immunoblotting. All subjects were Caucasians and their liver cadmium contents ranged from 0.11 to 3.95 μg/g wet weight, while their kidney cadmium contents were in the range of 2 to 63 μg/g wet weight. CYP1A2, CYP2A6, CYP2D6, CYP3A4, and CYP3A5 were detected in liver but not in kidney, and CYP1A1 and CYP1B1 were not found in liver or kidney. Lowered liver CYP2C8/19 protein contents were found to be associated with liver pathology. Importantly, we show elevated levels of CYP2C9 protein to be associated with cadmium accumulation in liver. No mechanism that explains this association is apparent, but there are two possibilities that require further study. One is that variation in CYP2C9 protein levels may be, in part, attributed to an individual's non-workplace exposure to cadmium, or an individual's CYP2C9 genotype may be a risk factor for cadmium accumulation. A positive correlation was found between liver CYP3A4 protein and subject age. Levels of liver CYP1A2 protein, but not other CYP forms, were increased in people more exposed to cigarette smoke, but there was no association between CYP1A2 protein and cadmium. CYP2A6 protein was found in all liver samples and CYP2A6 gene typing indicated the absence of CYP2A6 null allele (CYP2A6(D)) in this sample group, confirming very low prevalence of homozygous CYP2A6(D) in Caucasians. CYP2A6 gene types W/W, W/C, and C/C were not associated with variations in liver microsomal CYP2A6 protein. CYP2D6 protein was absent in all twenty-five kidney samples tested but was detectable in liver samples of all but two subjects, indicating the prevalence of the CYP2D6 null allele (CYP2D6(D)) in this sample group to be about 7%, typical of Caucasian populations.

Original languageEnglish
Pages (from-to)713-721
Number of pages9
JournalBiochemical Pharmacology
Volume62
Issue number6
DOIs
Publication statusPublished - Sep 15 2001
Externally publishedYes

Fingerprint

Kidney Cortex
Cadmium
Liver
Cytochrome P-450 Enzyme System
Cytochrome P-450 CYP2D6
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP1A2
Proteins
Kidney
Pathology
Smoke
Tobacco Products
Genes
Alleles
Weights and Measures
Cytochrome P-450 CYP1A1
Queensland
Immunoblotting
Autopsy
Protein Isoforms

Keywords

  • Cigarette smoke
  • CYP1A2 induction
  • Cytochrome P450
  • Environmental cadmium
  • Human autopsy
  • Individual differences
  • Tissue differences

ASJC Scopus subject areas

  • Pharmacology

Cite this

Relationships between non-occupational cadmium exposure and expression of nine cytochrome P450 forms in human liver and kidney cortex samples. / Baker, Jason R.; Satarug, Soisungwan; Reilly, Paul E B; Edwards, Robert J.; Ariyoshi, Noritaka; Kamataki, Tetsuya; Moore, Michael R.; Williams, David J.

In: Biochemical Pharmacology, Vol. 62, No. 6, 15.09.2001, p. 713-721.

Research output: Contribution to journalArticle

Baker, Jason R. ; Satarug, Soisungwan ; Reilly, Paul E B ; Edwards, Robert J. ; Ariyoshi, Noritaka ; Kamataki, Tetsuya ; Moore, Michael R. ; Williams, David J. / Relationships between non-occupational cadmium exposure and expression of nine cytochrome P450 forms in human liver and kidney cortex samples. In: Biochemical Pharmacology. 2001 ; Vol. 62, No. 6. pp. 713-721.
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