1,4-Dichlorobenzene-Induced Nephrotoxicity: Similarity with Unleaded Gasoline (UG)-Induced Renal Effects
1,4-Dichlorobenzene (1,4-DCB) administered (150 or 300 mg/kg/day, po) 5 days per week for 104 weeks caused a dose-related increase in the incidence of renal adenomas and/or carcinomas in male rats, but not female F-344 rats or either sex of B6c3f1 mice (NTP, 1987). 1,2-Dichlorobenzene (1,2-DCB), an isomer of 1,4-DCB, caused no increase in the incidence of male rat renal tumours (NTP, 1985); the doses used were, however, 2.5 times lower than those employed for the 1,4-DCB study. Exposure to vapours of unleaded gasoline (UG) for 114 weeks also produced a doserelated increase in the incidence of renal adenomas and carcinomas in male, but not female F-344 rats or either sex of mice (Kitchen, 1984). The incidence of male rat renal tumours was dose-dependent but relatively low for both compounds. Assessment of the genotoxic properties of 1,4-DCB and UG by a battery of tests has shown that the chemicals are nongenotoxic. Our hypothesis to explain renal tumour formation is based on a multi-stage carcinogenesis model: Cells, in which spontaneous DNA alterations naturally occur, replicate following chemically-induced cell proliferation causing a mutated cell. Mutated cells undergo clonal expansion due to increased cell proliferation. This greatly increases the likelihood of additional spontaneous mutations occurring, leading to an increased incidence of renal cancer.
KeywordsSodium Dodecyl Sulphate Renal Tumour Liver Cytosol National Toxicology Program B6C3F1 Mouse
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