Inhibition of neoplastic development in rat liver, kidney, oesophagus and forestomach by 4,4'-diaminodiphenylmethane administration

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Abstract
The modifying effects of 4,4'-diaminodiphenylmethane (DDPM) (0.1% in diet) administration on liver carcinogenesis induced by 2-acetylaminofluorene (2-AAF) (0.02% in diet), 3-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) (0.06% in diet), diethylnitrosamine (DEN) (0.001% in drinking water) and N -ethyl- N -hydroxyethylnitrosamine (EHEN) (0.1% in drinking water), EHEN-induced oesophagus and kidney carcinogenesis and forestomach carcinogenesis induced by butylated hydroxyanisole (1.0% in diet) were examined in F344 male rats. Mean survival time tended to be longer in DDPM-supplemented groups, the difference being significant in DEN + DDPM and EHEN + DDPM groups. Intake of carcinogens was slightly but not significantly reduced by DDPM. The incidences of hyperplastic nodules and hepato-cellular carcinomas were significantly decreased in 2-AAF or 3'-Me-DAB + DDPM groups. Pulmonary metastases were also less common in 3'-Me-DAB or EHEN + DDPM groups. Development of papillomas in the oesophagus but not in tumours in the forestomach was also inhibited by DDPM. Inhibition in the different organs was not significantly related to decrease in body weight or carcinogen intake, indicating a mechanism independent of non-specific toxic effects or reduction in food consumption. Some other factors possibly related to its ability to cause bile duct proliferation and/or altered activity of enzymes relevant to drug metabolism may be involved.

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