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

Baker, JR, Satarug, S, Reilly, PEB, Edwards, RJ, Ariyoshi, N, Kamataki, T, Moore, MR and Williams, DJ (2001) Relationships between non-occupational cadmium exposure and expression of nine cytochrome P450 forms in human liver and kidney cortex samples. Biochemical Pharmacology, 62 6: 713-721. doi:10.1016/S0006-2952(01)00716-X


Author Baker, JR
Satarug, S
Reilly, PEB
Edwards, RJ
Ariyoshi, N
Kamataki, T
Moore, MR
Williams, DJ
Title Relationships between non-occupational cadmium exposure and expression of nine cytochrome P450 forms in human liver and kidney cortex samples
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
Publication date 2001-01-01
Sub-type Article (original research)
DOI 10.1016/S0006-2952(01)00716-X
Volume 62
Issue 6
Start page 713
End page 721
Total pages 9
Place of publication Oxford, UK
Publisher Pergamon-Elsevier Science Ltd
Collection year 2001
Language eng
Subject C1
321299 Public Health and Health Services not elsewhere classified
730200 Public Health
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 kg/g wet weight, while their kidney cadmium contents were in the range of 2 to 63 mug/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 CYPIA2 protein, but not other CYP forms, were increased in people more exposed to cigarette smoke, but there was no association between CYPIA2 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, WIC, and CIC 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. (C) 2001 Elsevier Science Inc. All rights reserved.
Keyword Pharmacology & Pharmacy
Human Autopsy
Environmental Cadmium
Cytochrome P450
Individual Differences
Tissue Differences
Cigarette Smoke
Cyp1a2 Induction
In-vivo
Metallothionein Levels
Genetic-polymorphism
Caffeine Metabolism
Lung-cancer
Frequency
Japanese
Smoking
Enzymes
Disease
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
 
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Created: Wed, 15 Aug 2007, 01:49:49 EST