US EPA

2156390 

Journal Article 

Abstract 

Potentiation of carbon-tetrachloride hepatotoxicity by polychlorinated biphenyls 

Carlson, GP 

1974 

1 

Toxicology and Applied Pharmacology
ISSN: 0041-008X
EISSN: 1096-0333 

29 

1 

102 

English 

WOS:A1974T653800075 

is part of a larger document 3378179 Abstracts of papers for the Thirteenth Annual Meeting of the Society of Toxicology, Washington, D.C. March 10–14, 1974

Polychlorinated biphenyls (PCB's) have been recognized as widespread pollutants of the environment. Since PCB's have been shown to be inducers of drug metabolism, it was of interest to ascertain if they increase the toxicity of carbon tetrachloride (CCJ4) as phenobarbital (PB) does since the cytochrome P-450 species induced by PCB treatment differs from that induced by PB and also from that induced by 3-methylcholanthrene, an agent which protects against CCl4 hepatotoxicity. Adult male Charles River rats were injected ip daily with either corn oil or 25 mg/kg of Arochlor 1254 for 6 days. On the seventh day they were exposed to CCl4 (3600-4200 ppm) for 2 hr in a dynamic inhalation chamber and were sacrificed 24 hr later. Administration of Arochlor 1254 resulted in an increase in the liver-to-body weight ratio which was further increased by exposure to CCl4. Pretreatment with this PCB resulted in a significantly greater decrease in glucose-6-phosphatase activity following CC14 exposure than. in the controls. No elevations in serum glutamic pyruvic transaminase (SGPT) or serum glutamic oxalacetic transaminase (SGOT) activity were found with the Arochlor alone but this compound potentiated the rises due to CC14 5-fold. Arochlor 1254 significantly increased p-nitroanisole demethylation, cytochrome c reductase activity and cytochrome P-450 content. Subsequent exposure to CC14 resulted in a 72% decrease in p-nitroanisole demethylation and a 88% decrease in cytochromeP-450. In the controls these values were decreased by 43 and 41% respectively. In neither group was cytochrome c reductase altered by the CC14 exposure. The potentiation of CCl4 hepatotoxicity was further evidenced by histological observations which revealed slight to moderate damage in the livers of the controls but massive necrosis in the Arochlor group. (Supported by NIEHS Grant No. 00596.) 

Thirteenth Annual Meeting of the Society of Toxicology 

Washington, D.C. 

March 10–14, 1974