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Prolonged supplementation of vitamins A and E (2500 IU and 11.3 IU/rat daily) in 10.3% and 21.6% fatty diets administered to methylnitrosourea-induced Sprague-Dawley rats caused alterations in plasma and liver levels of both vitamins as well as of the total lipids. Liver vitamin A levels increased steadily (more than four-fold) until termination of the experiment, whereas plasma vitamin A levels only showed a minor increase at the end of the study in comparison to rats fed a standard diet. Liver vitamin E levels initially showed no difference from those of rats treated with a standard diet, and were decreased at the end of the experiment, whereas the respective plasma levels were increased throughout the study, only showing a decrease relative to initial values at termination of the experiment. Plasma total lipids increased with age and following supplementation of the vitamins in the high-fat diet, whereas liver total lipids were influenced less by aging than by the fat and vitamin contents of the respective diets. The observed alterations were, however, not related to significant chemopreventive activity of the vitamins A and E contained in high-fat diets.

Mammary tumor development induced by methylnitrosourea in female Sprague-Dawley rats had no significant effect on hepatic glutathione levels. If the diets of methylnitrosourea-treated animals were supplemented with vitamin A and E an increased hepatic glutathione level was observed initially. A high fat diet (21% per weight) supplemented with the two vitamins led to a decreased hepatic glutathione level 2 months after tumor induction. Advanced tumor development under any of the diets tested had no effect on hepatic glutathione.

Diethylstilbestrol-3,4-oxide (DES-3,4-oxide), one of the possible cancerogenic metabolites of the well-known estrogen diethylstilbestrol (DES), is a potential estrophilic cytostatic compound. It shows a very good affinity to the estrogen receptor. The uterotrophic activity determined in the mouse uterine weight bioassay is nearly identical with that of DES. Potential alkylating properties could neither be detected in the p-NBP test nor in the prophage induction test. DES-3,4-oxide [0.01–1.0 mg/kg body weight (b. wt.)] markedly inhibited the growth of the DMBA-induced hormone-dependent mammary carcinoma of the SD rat, as well as the growth of a hormone-dependent postmenopausal (but not of a premenopausal) human mammary carcinoma serially transplanted in nude mice. However, DES-3,4-oxide had not significantly better effect on the DMBA-induced mammary carcinoma of the SD rat than DES.

Specific receptors for PG, but not for DHT, could be demonstrated in the cytosol of a feline mammary carcinoma.

Short-term treatment of N-methyl-N-nitrosourea-induced mammary carcinomas in Sprague-Dawley rats with estradiol-linked nitrosoureas shows that the compounds in which the cytotoxic group is linked to position 17 of estradiol are superior to the 3-ester analogue. Moreover, N-(2-chloroethyl)-N-nitroso-carbamoyl (CNC)-l-alanyl-l-alanine-estradiol-3-ester is more effective and less toxic than CNC-l-alanine-estradiol-3-ester, being equivalent to ovariectomy in its therapeutic efficacy. Unlinked CNC-amino acid or-dipeptide in admixture with estradiol is less effective. Linked compounds at therapeutic dosages display estrogenic activity.