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The effect of chemical aging on the bioavailability and subsequent genotoxicity of coal tar (CT)-contaminated soils was evaluated in a 17-day feeding study using Fischer 344 male rats. Rats consumed a control diet or diets amended with soil, 0.35% CT, or soil freshly prepared or aged for 9 months with 0.35% CT. Mild treatment-related microscopic lesions in liver tissue and elevated enzyme levels in serum were detected in all CT treatment groups. The 32P-postlabeling assay was employed to determine DNA adduct formation in treated animals. All CT treatment groups induced DNA adducts in both the liver and lung. Adduct levels were 3-fold higher in lung DNA compared to hepatic DNA. After correcting adduct levels for total ingested polycyclic aromatic hydrocarbons (PAHs), a significant decrease (p < 0.05) in adduct levels was observed in both CT/soil treatment groups compared to CT control in liver and lung DNA. Adduct profiles of 32P-postlabeled hepatic and lung DNA displayed several nonpolar DNA adducts that comigrated with PAH-adducted calf thymus DNA standards as determined through both thin-layer chromatography (TLC) and high-pressure liquid chromatography (HPLC). These results suggest that soil, but not aging of contaminants in soil, decreases the bioavailability of genotoxic components in CT, as evidenced by DNA adduct analysis. [ABSTRACT FROM PUBLISHER]

Chloroform, generally regarded as a non-genotoxic compound, is associated with the induction of liver and/or kidney tumors in laboratory mice and rats. In particular, chloroform produced renal tubule tumors in low incidence in male Osborne-Mendel rats when administered by corn-oil gavage or in the drinking water. There is a lack of data on intermediate endpoints that may be linked to renal cancer development in this strain of rat, in contrast to mice. Specifically, evidence linking chloroform-induced liver and kidney tumors in mice with cytotoxicity and regenerative cell proliferation is very strong, but weak in the rat. In the present study, kidney tissue from a carcinogenicity bioassay of chloroform in Osborne-Mendel rats was re-evaluated for histological evidence of compound-induced cytotoxicity and cell turnover. All rats treated with 1800 ppm (160 mg/kg/day, high-dose group) in the drinking water for 2 years and half the rats treated with 900 ppm (81 mg/kg/day) had mild to moderate changes in proximal convoluted tubules in the mid to deep cortex indicative of chronic cytotoxicity. Tubule alterations specifically associated with chronic chloroform exposure included cytoplasmic basophilia, cytoplasmic vacuolation, and nuclear crowding consistent with simple tubule hyperplasia. Occasional pyknotic cells, mitotic figures in proximal tubules, and prominent karyomegaly of the renal tubule epithelium were present. These alterations were not present in control groups or at the 200-ppm (19 mg/kg/day) or 400-ppm (38 mg/kg/day) dose levels. This new information adds substantially to the weight of evidence that the key events in chloroform-induced carcinogenicity in rat kidney include sustained cellular toxicity and chronic regenerative hyperplasia. [ABSTRACT FROM PUBLISHER]