LIFETIME DOSE-RESPONSE RELATIONSHIPS FOR MAMMARY-TUMOR INDUCTION BY A SINGLE ADMINISTRATION OF N-METHYL-N-NITROSOUREA

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (5) , 1690-1694
Abstract
Dose-response relationships for the induction of mammary tumors by a single i.v. injection of N-methyl-N-nitrosourea (MNU) were studied. At 50 days of age, groups of 20 virgin female Sprague-Dawley rats received single doses of 50, 45, 40, 35, 30, 25, 20, 15 or 10 mg MNU per kg body wt; a group of 10 control rats received 0.85% NaCl solution only. Animals were observed for the appearance of mammary tumors over their life span or until 600 days after carcinogen administration. Malignant and benign mammary tumors appeared in all groups; malignant tumors appeared earlier and at a faster rate than did benign tumors. Incidence of cancer and number of cancers per animal increased with increasing MNU dose; the latent period for cancer increased with decreasing dose. The number of benign tumors induced as a percentage of total tumors increased with decreasing dose, ranging from .apprx. 10% in groups receiving > 30 mg MNU/kg to 58% in the group receiving 10 mg/kg. Foci of metastatic mammary carcinoma were found in lungs of animals in several MNU dose groups. A single i.v. administration of MNU induces mammary cancer in a dose-related fashion, with little toxicity and a short latent period; induced cancers metastasize to distant sites. The single-dose MNU model thus appears to be superior to the 7,12-dimethylbenz(a)anthracene and multiple-dose MNU models, particularly for use in studies of modification of mammary carcinogenesis.