Decreased incidence of diphenylamine-induced renal papillary necrosis in Syrian hamsters given dimethylsulphoxide.

The renal papillotoxicity of diphenylamine dissolved in dimethylsulphoxide (DMSO) was investigated in male Syrian hamsters, male Sprague-Dawley rats and female Mongolian gerbils. When diphenylamine in DMSO was administered orally to male Syrian hamsters (400, 600 or 800 mg/kg body weight/day for up to 9 days), the incidence of renal papillary necrosis was almost zero. Hamsters pretreated with DMSO (0.5 ml/100 g body weight/day) and 1 hr later given 400, 600 or 800 mg diphenylamine in peanut oil/kg body weight/day for 3 consecutive days had significantly reduced incidences of renal papillary necrosis (0/10, 0/10 and 1/10 in the low-, mid- and high-dose groups, respectively) when compared with hamsters given similar doses of diphenylamine but not pretreated with DMSO (5/10, 7/10 and 5/10 in the low-, mid- and high-dose groups, respectively). Focal, apex-limited renal papillary necrosis was observed in two Sprague-Dawley rats given 800 mg diphenylamine in DMSO/kg body weight/day orally for 9 days. Focal, intermediate renal papillary necrosis was observed in two additional rats administered 800 mg diphenylamine in DMSO/kg/day orally for 9 days. Renal papillary necrosis was not observed in any of the Mongolian gerbils. The results of these studies suggest that DMSO protects against diphenylamine-induced renal papillary necrosis in male Syrian hamsters.

Effect of Japanese seaweed (Laminaria angustata) extracts on the mutagenicity of 7,12-dimethylbenz[a]anthracene, a breast carcinogen, and of 3,2'-dimethyl-4-aminobiphenyl, a colon and breast carcinogen.

Animal model studies suggest that diets containing Laminaria angustata, a brown seaweed commonly eaten in Japan, inhibit breast carcinogenesis. In order to identify the compound(s) in the seaweed responsible for tumor-inhibiting activity, we used Ames/mammalian microsome assay system to determine the antimutagenic (or anticarcinogenic) effect of various solvents and water extracts of Laminaria angustata. The antimutagenic effects of acetone, ether, chloroform, chloroform + methanol, hot water and cold water extracts on the mutagenicity induced by 7,12-dimethylbenz[a]anthracene (DMBA), a breast carcinogen, and 3,2'-dimethyl-4-aminobiphenyl (DMAB), a colon and breast carcinogen, was studied using the Salmonella typhimurium strains TA98 and TA100. All extracts were nonmutagenic in both bacterial tester strains. The addition of 10-100 mg solvent extracts of seaweed/plate greatly inhibited DMAB-induced mutagenicity in both tester strains (80-96% inhibition) and DMBA-induced mutagenicity in TA100 (about 82%), whereas hot and cold water extracts produced a moderate inhibition in a dose-related manner in both strains.

Effect of micronutrients, antioxidants and related compounds on the mutagenicity of 3,2'-dimethyl-4-aminobiphenyl, a colon and breast carcinogen.

The possible antimutagenic effects of butylated hydroxytoluene (BHT), ethoxyquin, disulfiram, indole-3-carbinol, indole-3-acetonitrile, sodium selenite and alpha-tocopherol on 3,2'-dimethyl-4-aminobiphenyl-induced mutagenicity were studied using the Ames Salmonella/mammalian microsome assay system with strains TA98 and TA100. All seven compounds were nonmutagenic in both bacterial tester strains. The addition of or 50-250 micrograms of sodium selenite, 5-50 mg of alpha-tocopherol or 50-250 microgram of BHT per plate inhibited DMAB-induced mutagenicity in TA98 and/or TA100. Ethoxyquin, disulfiram and indole-3-carbinol increased DMAB-induced mutagenicity in TA100, whereas these compounds had little or no effect in TA98-3-acetonitrile had very little effect in either strain.

Effect of butylated hydroxytoluene and butylated hydroxyanisole on the mutagenicity of 3,2'-dimethyl-4-aminobiphenyl.

This study was undertaken to investigate the possible antimutagenic effects of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) on 3,2'-dimethyl-4-aminobiphenyl (DMAB)-induced mutagenicity, using the Ames Salmonella/mammalian microsome system. The addition of 100-250 micrograms of BHT or 25-500 micrograms of BHA/plate was found to inhibit DMAB-induced mutagenicity in Salmonella strains TA 98 and TA 100. In TA 100, the mutagenicity was further inhibited with the addition of S9 prepared from the livers of rats fed a 0.6% BHT diet as compared to S9 from the animals fed a diet containing no BHT.