title: Effect of prenatal and prepubertal genistein exposure on N-methyl-N-nitrosourea-induced mammary tumorigenesis in female Sprague-Dawley rats.
abstract: BACKGROUND
  The effect of prenatal and prepubertal genistein exposure on the development of chemically-induced mammary carcinomas in rat was investigated.
  
  
  METHODS
  Genistein was subcutaneously (s.c.) injected daily, from gestational days 15 to 19, into pregnant Sprague-Dawley rats at 0, 1.5 or 30 mg/kg/day. Female offspring of mothers not exposed to genistein during pregnancy received daily s.c. injection, from prepubertal days 15 to 19, at a dose of 1.5 or 30 mg/kg/day. At 28 days of age, 6 female offspring from each group were sacrificed to observe the influence of genistein and the remaining rats were injected intraperitoneally with 50 mg/kg N-methyl-N-nitrosourea (MNU). Rats injected with MNU were sacrificed at 26 weeks of age or when their largest mammary tumor was > or = 1 cm in size.
  
  
  RESULTS
  At the time when MNU was administered, the different groups had comparable mammary gland development; genistein-treated and -untreated rats had similar numbers of terminal end buds (TEBs) at the periphery of the mammary glandular tree. However, estrogen receptor alpha (ER alpha)- and progesterone receptor (PgR)-positive cells, p63-positive cells and proliferating cell nuclear antigen (PCNA)-labeling index were lower in genistein-exposed TEBs. Although tumor multiplicity and latency were not significant, prenatal or prepubertal genistein exposure, at low or high dosage, tended to suppress the incidence of mammary carcinomas > or = 1 cm; suppression was significant in the prepubertal low-dose group.
  
  
  CONCLUSIONS
  The majority of the mammary carcinomas in the present study were hormone-dependent. The present findings suggest that administration of genistein in the perinatal period has protective effects against MNU-induced mammary carcinoma in Sprague-Dawley rats, via reduction of levels of ER alpha- and/or PgR-positive cells (presumed progenitor cells of mammary carcinomas), p63-positive mammary progenitor/stem cells (involved in cell renewal) and PCNA-positive cells (necessary for cell proliferation).
authors.affiliation: Department of Pathology II, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan.
authors.forename: Ren-Jeng
authors.initials: RJ
authors.lastname: Pei
authors.forename: Mutsuya
authors.initials: M
authors.lastname: Sato
authors.forename: Takashi
authors.initials: T
authors.lastname: Yuri
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Danbara
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Nikaido
authors.forename: Airo
authors.initials: A
authors.lastname: Tsubura
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D047628:Estrogen Receptor alpha; D005260:Female; D019833:Genistein / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008770:Methylnitrosourea / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012741:Sexual Maturation / Q000187:drug effects; D014621:Vagina / Q000187:drug effects / Q000254:growth & development
chemical_list: D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D002273:Carcinogens; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D008770:Methylnitrosourea; D019833:Genistein