Effects of chloroform and bromodichloromethane on DNA synthesis in male F344 rat kidney.
We have been investigating the actions of chloroform (CHCl3) and bromodichloromethane (BDCM) in rat kidney after different routes of exposure. Male F344 rats were exposed by gavage with corn oil or water as the diluting vehicle. All experiments lasted 30 days with gavage exposures 5 days per week for 4 weeks (20 doses). All animals were injected IP with bromodeoxyuridine (BrdU) 3 times over a 6-day period at 50 mg/kg/injection. Kidney tissue was fixed and slides were stained with hematoxylin and eosin for routine viewing and by the PAP (peroxidase-antiperoxidase) technique using anti-BrdU to label cells in DNA synthesis. There were no significant changes in gross parameters evaluated between the control rats and the rats exposed to CHCl3 or BDCM. Rats exposed via corn oil gavage to CHCl3 displayed a segment-specific epithelial cell necrosis (6/6 high dose, 2/6 low dose). The lesions were primarily localized to the second segment of the proximal tubule, although some spread to cells in the first segment was occasionally observed. No histologic lesions were observed in the kidneys of rats exposed to BDCM. Preliminary results indicate a significant increase in DNA synthesis in the CHCl3-treated rats and a slight increase in DNA synthesis in BDCM-treated rats with corn oil as the diluent. The increase in BrdU labeling was primarily in cells of the S2 segment of the proximal tubule and interstitial cells of CHCl3-exposed animals and in cells of the S3 segment of BDCM-exposed animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pathology, University of Maryland School of Medicine, Baltimore 21201.
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Lipsky
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Skinner
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O'Connell
D000284:Administration, Oral; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D002725:Chloroform / Q000008:administration & dosage / Q000633:toxicity*; D003314:Corn Oil; D004247:DNA / Q000096:biosynthesis*; D006846:Hydrocarbons, Halogenated / Q000008:administration & dosage / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D022882:Trihalomethanes; D014867:Water
D002273:Carcinogens; D006846:Hydrocarbons, Halogenated; D022882:Trihalomethanes; D014867:Water; C025191:bromodichloromethane; D002725:Chloroform; D003314:Corn Oil; D004247:DNA; D001973:Bromodeoxyuridine