N-methyl-N-nitrosourea-induced mammary carcinogenesis is promoted by short-term treatment with estrogen and progesterone mimicking pregnancy in aged female Lewis rats.
We examined the effects of short-term estrogen and progesterone treatment mimicking pregnancy in aged female Lewis rats on the development of N-methyl-N-nitrosourea (MNU)-induced mammary carcinoma. Rats were administered a single intraperitoneal injection of 20 mg/kg MNU at 7 weeks of age and half of those rats were administered a subcutaneously implanted 21-day release pellet containing 0.5 mg 17beta-estradiol and 32.5 mg progesterone (E/P) at 24 weeks of age. The rats were then monitored for the occurrence of mammary tumors. Rats were sacrificed when the largest mammary tumor became > or = 1 cm in diameter, or when the rat reached 48 weeks of age. Development of MNU-induced mammary carcinomas was accelerated after short-term E/P treatment, compared with E/P-untreated rats: the incidence of > or = 1-cm mammary carcinomas tended to increase (60 vs. 44%); the latency tended to shorten (28.7 vs. 34.6 weeks); and cancer multiplicity (number of all-sized carcinomas per rat) significantly increased (1.8 vs. 0.8). In E/P-treated rats, comedo necrosis was frequently seen and the incidence of estrogen receptor and/or progesterone receptor-negative mammary carcinomas was significantly increased. Early age at full-term pregnancy or short-term hormone treatment mimicking pregnancy may suppress the risk of breast cancer, but the age of hormone exposure is a crucial factor, because hormone exposure mimicking pregnancy in aged individuals may exert effects opposite of those exerted in younger individuals.
Tsukamoto
Reiko
R
Department of Pathology II, Kansai Medical University, Osaka 570-8506, Japan.
Mikami
Takako
T
Miki
Katsuaki
K
Uehara
Norihisa
N
Yuri
Takashi
T
Matsuoka
Yoichiro
Y
Okazaki
Kazuichi
K
Tsubura
Airo
A
D000375:Aging; D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D004338:Drug Combinations; D004343:Drug Implants; D004958:Estradiol / Q000627:therapeutic use*; D005260:Female; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008770:Methylnitrosourea / Q000633:toxicity*; D009336:Necrosis; D011247:Pregnancy; D011374:Progesterone / Q000627:therapeutic use*; D051381:Rats; D011917:Rats, Inbred Lew; D015430:Weight Gain / Q000187:drug effects
D000477:Alkylating Agents; D004338:Drug Combinations; D004343:Drug Implants; D011374:Progesterone; D004958:Estradiol; D008770:Methylnitrosourea