Effects of 17 β-Estradiol and Diethylstilbestrol on Concurrent Development of Hepatic, Mammary, and Pituitary Tumors in WF Rats: Evidence for Differential Effect on Liver

• Published in: JNCI : Journal of the National Cancer Institute 1984-11, Vol.73 (5), p.1229-1234
• Main Authors: Sumi, Chiyo, Yokoro, Kenjiro, Matsushima, Ryotaro
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Body Weight - drug effects; Carcinogens; Castration; Diethylstilbestrol - pharmacology; Drug toxicity and drugs side effects treatment; Estradiol - pharmacology; Liver Neoplasms - chemically induced; Liver Neoplasms - pathology; Male; Mammary Neoplasms, Experimental - chemically induced; Mammary Neoplasms, Experimental - pathology; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Nitrosourea Compounds; Organ Size - drug effects; Organ Specificity; Pharmacology. Drug treatments; Pituitary Neoplasms - chemically induced; Pituitary Neoplasms - pathology; Rats; Rats, Inbred Strains
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/73.5.1229

17β-Estradiol [(E2) CAS: 50-28-2; estradiol] and diethylstilbestrol [(DES) CAS: 56-53-1 α-α′-diethyl-4,4′-stilbenediol] were compared to determine their tumor-inducing abilities in tissue. After castration at 40 days of age, inbred male WF rats received a pellet of either 5.0 mg DES or 5.0 mg E2. Approximately half of the rats that had been given DES or E2 were further given at 50–55 days of age 5.0 mg N-nitrosobutylurea [(NBU) CAS: 869-01-2; 1-butyl-1-nitrosourea] in their drinking water each day for 30 days. None of the castrated rats given E2 alone developed hepatic tumors (HT). Even further addition of NBU did not elicit any HT. Conversely, E2 treatment as well as DES treatment, whether administrated alone or in combination with NBU, resulted in an increase in the incidence of pituitary tumors (PT) and in the mean pituitary weight. The data indicate that E2 was ineffective in inducing HT in castrated male rats, whereas E2 showed an ability to induce PT similar to that of DES. In addition, E2 was not as able to induce as many mammary tumors as DES was able to induce. There was no significant synergism between E2 and NBU in contrast to that between DES and NBU in mammary tumorigenesis, whereas these two estrogens had a similar effect in causing an increase in the pituitary weight. This study, therefore, suggests that the carcinogenic effect of estrogens may not always correlate with their estrogenic effect and further confirms the noninvolvement of prolactin in hepatic tumorigenesis.