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657248 
Journal Article 
Trihalomethane induced alterations in the content of metallothionein and in the activities of heme metabolizing enzymes in rats 
Ariyoshi, T; Yamaguchi, M; Miyazaki, Y; Arizono, K 
1993 
Yes 
Bulletin of Environmental Contamination and Toxicology
ISSN: 0007-4861
EISSN: 1432-0800 
NIOSH/00213239 
50 
5 
772-778 
English 
8490284 
WOS:A1993KR26000021 
The effects of trihalomethanes on hepatic metallothionein and heme metabolizing enzymes were studied in rats. Male Wistar-rats were administered 408mg/kg bromoform (75252), 192mg/kg chloroform (67663), 86mg/kg bromodichloromethane (75274) (BDCM), or 74mg/kg dibromochloromethane (124481) (DBCM) orally. Selected rats were killed 6, 12, 24, or 48 hours after dosing and the livers were removed and assayed for metallothionein, delta-aminolevulinic-acid-synthetase (ALA), heme-oxygenase, and cytochrome-P-450 (P450). Other rats were given 204mg/kg bromoform or 37mg/kg DBCM daily for 7 days. They were killed 1 day after the last exposure and weighed. Their livers were analyzed for metallothionein, P450, ALA, and heme-oxygenase. Following single dosing, hepatic metallothionein concentrations were significantly increased 6 and 12 hours after exposure to chloroform and bromoform and 12 hours after exposure to BDCM and DBCM. The magnitude of the increases were larger after treatment with the more chlorinated compounds. ALA activity was significantly increased 12 and 24 hours after treatment with all compounds except at 12 hours after chloroform. ALA activity was still elevated 48 hours after exposure to bromoform and DBCM. All compounds significantly increased heme-oxygenase activity 6, 12, and 24 hours after dosing except for BDCM which had no effect at 6 hours. Heme-oxygenase activity was still elevated 48 hours after chloroform. Hepatic P450 content was significantly decreased by chloroform and bromoform, the effect of chloroform being greater. BDCM had no effect. DBCM caused slight decreases in P450 content at 12 and 24 hours. Seven days treatment with bromoform and DBCM did not significantly alter body or liver weight or hepatic metallothionein or P450 content or ALA or heme-oxygenase activity. The authors suggest that the effects of trihalomethanes on hepatic P450 content may reflect stimulation of processes involving heme degradation or inhibition of processes involving heme utilization. 
5-Aminolevulinate Synthetase;drug effects;metabolism;Animal;Chloroform;administration & dosage;toxicity;Cytochrome P-450;analysis;Heme Oxygenase (Decyclizing);Hydrocarbons;Brominated;Halogenated;Liver;chemistry;enzymology;Male;Metallothionein;Rats;Wistar