EFFECTS OF CHLOROFORM AND BROMODICHLOROMETHANE ON RNA-SYNTHESIS IN MALE F344 RAT-KIDNEY

We have been investigating the actions of chloroform (CHCl3) and bromo dichloromethane (BDCM) in rat kidney after different routes of exposur e. Male F344 rats were exposed by gavage with corn oil or water as the diluting vehicle. All experiments lasted 30 days with gavage exposure s 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 hemat oxylin and eosin for routine viewing and by the PAP (peroxidase-antipe roxidase) technique using anti-BrdU to label cells in DNA synthesis. T here 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 c ell 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 hi stologic 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 BD CM-treated rats with corn oil as the diluent. The increase in BrdU lab eling 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. The rats exposed using water as the vehicle did not show significant pathology (except for one rat in the high-dose CHCl3 group, which had mild necrosis of proximal tubule epit helium). There were no changes in DNA synthesis in the CHCL(3)-treated rat kidneys when water was used as the vehicle. There was a slight in crease in total DNA synthesis in the BDCM-treated rat kidneys, and the increase was mainly in the third segment of the proximal tubule. Thes e data indicate differences in histopathologic alterations and levels of DNA synthesis that appear to depend on the vehicle that the chemica ls were dissolved in and/or the route of administration. CHCl3-induced pathologic alterations were more severe in the animals exposed by cor n oil gavage. BDCM, an established renal carcinogen in rats, failed to induce any histopathologic alterations under the different experiment al conditions of this study.