title: Immuno-neutralization of circulating relaxin does not alter the breast cancer-protective action of parity in MNU-treated rats.
abstract: Early pregnancy and childbirth protects women against future development of breast cancer by an unknown mechanism. Parity likewise reduces mammary cancer incidence in rats exposed to the carcinogen, N-methyl-N-nitrosourea (MNU), providing a model for the human phenomenon. We hypothesized that relaxin, a 6KD luteal mammotropic hormone of pregnancy, might be the anti-cancer pregnancy factor, and that induced relaxin deficiency during rat gestation would restore carcinogen sensitivity. Forty-one pregnant (age 50 days) and 25 age-matched virgin Sprague-Dawley rats were used. Relaxin deficiency was induced by injecting mouse monoclonal anti-rat relaxin antibody (MCA1) days 12-18 of gestation. Pregnant controls were injected with vehicle or mouse IgG on the same schedule. Because MCA1 disrupts parturition, all rats underwent cesarean section on day 22. At age 100 days, all rats were injected i.v. with MNU (50mg/Kg) and examined daily for tumors until euthanized at age 240 days. Mammary tumor incidence and frequency were significantly (p<0.01) reduced and tumor latency was increased (p<0.001) in primiparous as compared with virgin rats. However, tumor incidence, type, size and latency were similar in MCA1-treated and control primiparous rats. Thus, luteal relaxin does not appear to be the factor responsible for resistance to breast cancer.
authors.affiliation: Department of Environmental Medicine, Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo10987, USA. steinetz@env.med.nyu.edu
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Steinetz
authors.forename: O David
authors.initials: OD
authors.lastname: Sherwood
authors.forename: Sally
authors.initials: S
authors.lastname: Lasano
authors.forename: Lori
authors.initials: L
authors.lastname: Horton
authors.forename: Maarten C
authors.initials: MC
authors.lastname: Bosland
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001723:Birth Rate; D002273:Carcinogens / Q000633:toxicity; D002584:Cervix Uteri / Q000502:physiology; D005260:Female; D007116:Immunization, Passive; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D008770:Methylnitrosourea / Q000633:toxicity; D010298:Parity; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012065:Relaxin / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D002273:Carcinogens; D008770:Methylnitrosourea; D012065:Relaxin