Tributyltin potentiates 3,3',4,4',5-pentachlorobiphenyl-induced cytochrome P-4501A-related activity.
Induction of cytochrome P-4501A protein and induction of related enzyme activity are hallmark physiological responses following exposure to planar halogenated aromatic hydrocarbons (HAHs) such as 3,3',4,4',5-pentachlorobiphenyl (PCB 126; PeCB). Environments contaminated by HAHs are often contaminated by mixtures of anthropogenic contaminants, including organometallic compounds. Both HAHs and organometallics easily bioconcentrate and bioaccumulate in aquatic food chains that may ultimately be linked to humans through seafood consumption. Tributyltin (TBT), a marine biocide, has been detected in many aquatic environments due to its primary use as a marine antifoulant agent. Exposure to TBT, as well as several PCBs, has been associated with immunotoxicity, neurotoxicity, and endocrine disruption. Recently TBT has been shown to inhibit cytochrome P-4501A activity in vitro, but information concerning these effects in vivo and in combination with classical inducers of P-4501A, such PeCB, is lacking. We exposed female B6C3F1 mice to 0.01, 0.1, and 1.0 mg/kg PeCB, TBT, or both in combination, with corn oil (CO) serving as a carrier control. Cytochrome P-4501A protein levels and related benzo[a]pyrene hydroxylation (BaP-OHase) activity were measured following a single acute intraperitoneal (ip) dose or seven daily injections. Body, thymus, and liver weights were used to monitor general physiological responses following exposure. P-4501A levels and BaP-OHase activity were significantly elevated in mice exposed to PeCB alone. This effect was enhanced by coexposure to low levels of TBT; PeCB-induced P-4501A-related activity was potentiated at the low range of each. The highest dose of TBT, however, inhibited these activities when given in combination with PeCB. Thymic atrophy was evident only in mice exposed daily to 0:1 and 1.0 mg/kg PeCB alone, or to a combination of the lowest and highest dose of PeCB and TBT, respectively. Because environmental levels of TBT are not expected to be as high as the highest level used in our toxicological studies, we conclude that environmental exposure to TBT may potentiate, rather than inhibit, the activity of environmental levels of HAHs that are associated with P-4501A induction.
DeLong
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Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, MS 39762-9825, USA.
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D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D008099:Liver / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology; D014220:Trialkyltin Compounds / Q000633:toxicity*
D014220:Trialkyltin Compounds; C011559:tributyltin; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; C023035:3,4,5,3',4'-pentachlorobiphenyl