Contribution of methylmercury, polychlorinated biphenyls and organochlorine pesticides to the toxicity of a contaminant mixture based on Canadian Arctic population blood profiles.
Human populations are simultaneously exposed to a variety of anthropogenic contaminants. However, despite extensive literature on animal exposure to single compounds, data on the toxicity of complex mixtures are scarce. The Northern Contaminant Mixture (NCM) was formulated to contain the 27 most abundant contaminants in the same relative proportions found in the blood of Canadian Arctic populations. Sprague-Dawley rat dams were dosed from the first day of gestation until weaning with methylmercury (MeHg), polychlorinated biphenyls (PCBs) or organochlorines pesticides (OCs) administered either separately or together in the NCM. An additional control group for hypothyroxinemia was included by dosing dams with the goitrogen 6-propyl-2-thiouracil (PTU). Offspring growth, survival, serum thyroxine and Thyroid Stimulating Hormone (TSH) levels, thyroid gland morphology, brain taurine content and cerebellum and hippocampus protein expression patterns resulting from such exposures were monitored. Pups' increased mortality rate and impaired growth observed in the NCM treatment group were attributed to MeHg, while decreased circulating thyroxine levels and perturbations of thyroid gland morphology were mostly attributable to PCBs. Interestingly, despite comparable reduction in serum thyroxine levels, PCBs and PTU exposures produced markedly different effects on pup's growth, serum TSH level and brain taurine content. Analysis of cerebellum and hippocampus protein expression patterns corroborated previous cerebellum gene expression data, as contaminant co-exposure in the NCM significantly masked the effects of individual components on protein two-dimensional electrophoresis patterns. Identification by MALDI-TOF/TOF MS of differentially expressed proteins involved notably in neuronal and mitochondrial functions provided clues on the cellular and molecular processes affected by these contaminant mixtures.
Pelletier
Guillaume
G
Hazard Identification Division, Environmental Health, Science and Research Bureau, Chemicals Management Directorate, Health Canada, Canada. guillaume_pelletier@hc-sc.gc.ca
Masson
Sheila
S
Wade
Mike J
MJ
Nakai
Jamie
J
Alwis
Ramona
R
Mohottalage
Susantha
S
Kumarathasan
Premkumari
P
Black
Paleah
P
Bowers
Wayne J
WJ
Chu
Ih
I
Vincent
Renaud
R
D000367:Age Factors; D000818:Animals; D001110:Arctic Regions; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002170:Canada; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D045424:Complex Mixtures / Q000633:toxicity*; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005865:Gestational Age; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006843:Hydrocarbons, Chlorinated / Q000097:blood / Q000633:toxicity*; D007037:Hypothyroidism / Q000097:blood / Q000139:chemically induced; D008297:Male; D008767:Methylmercury Compounds / Q000097:blood / Q000633:toxicity*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010575:Pesticides / Q000097:blood / Q000633:toxicity*; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000633:toxicity*; D011441:Propylthiouracil; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013654:Taurine / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013963:Thyroid Hormones / Q000097:blood; D014874:Water Pollutants, Chemical / Q000097:blood / Q000633:toxicity*
D045424:Complex Mixtures; D006843:Hydrocarbons, Chlorinated; D008767:Methylmercury Compounds; D024101:Mitochondrial Proteins; D009419:Nerve Tissue Proteins; D010575:Pesticides; D013963:Thyroid Hormones; D014874:Water Pollutants, Chemical; D013654:Taurine; D011441:Propylthiouracil; D011078:Polychlorinated Biphenyls