N-methyl-N-nitrosourea-induced mammary carcinogenesis is promoted by short-term treatment with estrogen and progesterone mimicking pregnancy in aged female Lewis rats

Reiko Tsukamoto, Takako Mikami, Katsuaki Miki, Norihisa Uehara, Takashi Yuri, Yoichiro Matsuoka, Kazuichi Okazaki, Airo Tsubura

Research output: Contribution to journalArticle

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Abstract

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 17β-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 ≥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 ≥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.

Original languageEnglish
Pages (from-to)337-342
Number of pages6
JournalOncology reports
Volume18
Issue number2
Publication statusPublished - Aug 1 2007
Externally publishedYes

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Methylnitrosourea
Progesterone
Estrogens
Carcinogenesis
Breast
Pregnancy
Breast Neoplasms
Therapeutics
Hormones
Incidence
Progesterone Receptors
Intraperitoneal Injections
Estrogen Receptors
Estradiol
Necrosis
Carcinoma

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

N-methyl-N-nitrosourea-induced mammary carcinogenesis is promoted by short-term treatment with estrogen and progesterone mimicking pregnancy in aged female Lewis rats. / Tsukamoto, Reiko; Mikami, Takako; Miki, Katsuaki; Uehara, Norihisa; Yuri, Takashi; Matsuoka, Yoichiro; Okazaki, Kazuichi; Tsubura, Airo.

In: Oncology reports, Vol. 18, No. 2, 01.08.2007, p. 337-342.

Research output: Contribution to journalArticle

Tsukamoto, Reiko ; Mikami, Takako ; Miki, Katsuaki ; Uehara, Norihisa ; Yuri, Takashi ; Matsuoka, Yoichiro ; Okazaki, Kazuichi ; Tsubura, Airo. / N-methyl-N-nitrosourea-induced mammary carcinogenesis is promoted by short-term treatment with estrogen and progesterone mimicking pregnancy in aged female Lewis rats. In: Oncology reports. 2007 ; Vol. 18, No. 2. pp. 337-342.
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