Carcinogenesis, Vol. 20, No. 4, 623-628,
April 1999
© 1999 Oxford University Press
Protective effects of pregnancy and lactation against N-methyl-N-nitrosourea-induced mammary carcinomas in female Lewis rats
Department of Pathology, Kansai Medical University, Moriguchi, Osaka 570-8506, Japan and
1 Cancer Research Laboratory, Department of Molecular and Cellular Biology, University of California, Berkeley, CA 94720, USA
The role of parity before and after N-methyl-N-nitrosourea (MNU) treatment in protection against mammary carcinogenesis was investigated. The effect of lactation on reduction in the incidence of mammary carcinoma was also examined. Parous rats were compared with respective age-matched virgins (AMVs). Pregnancy and lactation prior to MNU exposure significantly reduced both the incidence of mammary carcinoma (22 versus 72%) and the average number of mammary carcinomas per rat (0.22 versus 0.86) and significantly prolonged the latency of the carcinomas (247 versus 215 days). Pregnancy and lactation following MNU exposure also significantly reduced both the incidence of mammary carcinoma (25 versus 94%) and the average number of mammary carcinomas per rat (0.25 versus 1.50) and significantly prolonged the latency (240 versus 155 days). Lactation showed an additive effect on the reduction in mammary cancer. Pregnancy suppressed the number of estrogen receptor (ER)- and progesterone receptor (PgR)-positive cells and lowered the cell proliferation rate in the non-tumoral mammary glands. Since the majority (>76%) of the mammary carcinomas was hormone dependent in both the parous and AMV rats, pregnancy and lactation appear to decrease the ER- and/or PgR-positive cells presumed to be the progenitors of hormone-dependent carcinomas and they lowered the cell turnover necessary for tumor promotion in parous rats, resulting in a lower mammary carcinoma yield.
Abbreviations: AMV, age-matched virgin; ER, estrogen receptor; LSAB, labeled streptavidin–biotin; MNU, N-methyl-N-nitrosourea; PCNA, proliferating cell nuclear antigen; PgR, progesterone receptor.
2 To whom correspondence should be addressed Email: tsubura{at}takii.kmu.ac.jp
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