title: Biomarkers of cadmium and arsenic interactions.
abstract: Advances in proteomics have led to the identification of sensitive urinary biomarkers of renal dysfunction that are increasingly used in toxicology and epidemiology. Recent animal data show that combined exposure to inorganic arsenic (As) and cadmium (Cd) gives rise to more pronounced renal toxicity than exposure to each of the agents alone. In order to examine if similar interaction occurs in humans, renal dysfunction was studied in population groups (619 persons in total) residing in two metal contaminated areas in China: mainly a Cd contaminated area in Zhejiang province (Z-area) and mainly a As contaminated area in Guizhou province (G-area). Nearby control areas without excessive metal exposure were also included. Measurements of urinary beta(2)-microglobulin (UB2MG), N-acetyl-beta-glucosaminidase (UNAG), retinol binding protein (URBP) and albumin (UALB) were used as markers of renal dysfunction. Urinary Cd (UCd) and total As (UTAs) were analyzed by graphite-furnace atomic absorption spectrometry. Urinary inorganic As and its mono- and di-methylated metabolites (UIAs) were determined by Hydride generation. Results. As expected, the highest UCd values occurred in Z-area (Geometric mean, GM 11.6 microg/g crea) while the highest UTAs values occurred in G-area (GM = 288 microg/g crea). Statistically significant increases compared to the respective control area were present both for UTAs, UCd and for UB2MG, UNAG and UALB in Z-area as well as in G-area. UIAs was determined only in Z area. In G-area, there was a clear dose-response pattern both in relation to UTAs and UCd for each of the biomarkers of renal dysfunction. An interaction effect between As and Cd was demonstrated at higher levels of a combined exposure to As and Cd enhancing the effect on the kidney. In Z-area an increased prevalence of B2MG-uria, NAG-uria and ALB-uria was found in relation to UCd, but no relationship to UTAs was found. A statistically significant relationship between UIAs and UB2MG was found among women in this area and an interaction between As and Cd was indicated for B2MG. Conclusion. The present studies, which employed sensitive biomarkers of renal dysfunction, give support to the idea that human co-exposure to Cd and inorganic arsenic gives rise to more pronounced renal damage than exposure to each of the elements alone, but further studies are needed to establish and clarify this interaction.
authors.affiliation: Environmental Medicine, Umeå University, S-901 87 Umeå, Sweden. gunnar.nordberg@envmed.umu.se
authors.forename: G F
authors.initials: GF
authors.lastname: Nordberg
authors.forename: T
authors.initials: T
authors.lastname: Jin
authors.forename: F
authors.initials: F
authors.lastname: Hong
authors.forename: A
authors.initials: A
authors.lastname: Zhang
authors.forename: J P
authors.initials: JP
authors.lastname: Buchet
authors.forename: A
authors.initials: A
authors.lastname: Bernard
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine*; D000419:Albuminuria / Q000139:chemically induced*; D001151:Arsenic / Q000633:toxicity* / Q000652:urine; D015415:Biomarkers; D002104:Cadmium / Q000633:toxicity* / Q000652:urine; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008297:Male; D001613:beta 2-Microglobulin / Q000652:urine*
chemical_list: D015415:Biomarkers; D001613:beta 2-Microglobulin; D002104:Cadmium; D000118:Acetylglucosaminidase; D001151:Arsenic