The Promotional Environment for Mammary Carcinogenesis is Decreased in the Parous Rats Compared to that of Nulliparous Rats

Transplantation Studies. The tumorigenicity of MNU-treated MEC transplanted to virgin or parous Lewis rats was tested (41). The objective ofthese studies was to determine whether the systemic environment in the parous rat is supportive of tumorigenesis. Young nulliparous Lewis rats (50-60 days of age) were treated with MNU. One month after treatment, the treated mammary glands were removed and enzymatically dissociated. The purified epithelial cells were transplanted per site) to the subscapular fat pads of parous or age-matched virgins (AMV) hosts. MCs were found in 9/16 virgin hosts and in only 1/7 parous hosts within 6 mo of transplantation. These preliminary findings suggest that transformed MEC are capable of producing carcinomas when transplanted into virgin hosts, and that the systemic factors in the parous host have a decreased ability to support the promotion of transformed MEC to frank carcinomas.

Parous vs. Nulliparous Rats: Mammogenic Hormones and Mammary Epithelial Cells. Administration of MNU to 50-60-day old nulliparous rats, 120-day-old nulliparous rats, and 120-day-old parous rats, resulted in a high incidence of mammary cancers in the nulliparous rats (97 % in 50-60 day old rats; 75 % in 120 day old rats), no MCs developed in the parous rats (26). The concentrations in the serum of mammotropic hormones were measured at the time of MNU treatment. GH concentration was reduced in parous rats (16.1 ng/ml) compared to young nulliparous (59.3 ng/ml), and age matched nulliparous (38.6 ng/ml). PRL levels were 14.6 ng/ml in parous, 25.7 ng/ml in young nulliparous, and 25.5 ng/ml in age-matched nulliparous. Levels of E2, P, corticosterone, and thyroxine were not different in the three groups. The concentrations of ERa and EGFR were decreased in the mammary glands of parous rats (3.5 fmol/mg protein, 3,500 cpm/mg) compared to young nulliparous (12.1 fmol/mg, 5000 cpm/mg), and age-matched nulliparous (7.9 fmol/mg, 5000 cpm/mg). Concentrations of GH receptor were not significantly different among the 3 groups. These studies led us to hypothesize that protection from mammary cancer induced by pregnancy is not due to the loss of target cells for carcinogenesis but is due to a decrease in the systemic promotional environment.

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