Somatic mutation in the mammary gland: Influence of time and estrus

Sun Beichen, Naoko Shima, John A. Heddle

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16 Scopus citations


A critical factor in the quantitation of mutation induction in vivo is the time interval between treatment and sampling. In order to study mutagenesis in the mammary epithelium, the cell type in which breast cancer arises, we have measured the manifestation time, the minimum time required for the maximum mutant frequency to be achieved, in this tissue. The F1 LacZ transgenic mice (Muta(TM) Mouse x SWR) were treated with N-ethyl-N-nitrosourea (ENU) at 50 mg/kg for five consecutive days and then sampled at 1, 2, 4, 6, 9, or 12 weeks after the last treatment. The LacZ- mutant frequency reached a maximum at 4 weeks post-treatment and did not vary significantly thereafter. Dlb-1- mutations in the small intestine reached a maximum at 2 weeks after treatment and did not vary significantly thereafter. Since the stage of estrus cycle during carcinogen exposure influences the mammary tumor incidence and latency, it was expected that it would also affect mutation induction. To test this, F1 LacZ mice in the estrus or di-estrus stage were treated with an acute dose of 250 mg/kg ENU and sampled 10-13 weeks post-treatment. No statistical difference between the two groups was found, indicating that the effect of estrus on carcinogenesis is not due to variation in the sensitivity of the stage of the mammary gland to mutation. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Issue number1
StatePublished - Jun 1 1999

Bibliographical note

Funding Information:
This work was supported by grants from Cancer Research Society, the National Cancer Institute of Canada with funds from the Canadian Cancer Society, and Stratagene. We thank Hazleton Laboratory for permission to cross Muta™ Mouse to obtain F 1 . We are also grateful to Cesare Urlando, Jeniffer Moody, and William Cruz for their help with these experiments and Lidia Cosentino for her advice on the manuscript as well as help in experiments.


  • Dlb-1
  • LacZ transgene
  • Manifestation time
  • N-ethyl-N-nitrosourea
  • Small intestine


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