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The Sex-dependent Difference in the Development of Liver Tumors in Mice Administered Dimethylnitrosamine¹

Division of Oncology, The Chicago Medical School, Institute for Medical Research, Chicago, Illinois 60612

The objectives of the present investigation were to explore the effect of the dose of dimethylnitrosamine (DMN) on the induction of tumors in various tissues and evaluate the existence of a sex difference in development of liver tumors.

DMN was injected repeatedly at 3 dose levels into (C57BL x C3H)F₁ mice starting at 7 days of age. The injections were given i.p. at 3-day intervals for a total of 6 times. One, 2, or 4 µg of DMN were delivered/gm body weight at each injection. Mice were sacrificed when 66 weeks of age, at which time tumor response was evaluated.

The results showed positive dose-response relationship between the dose of DMN delivered and the incidence of hepatomas, hepatocarcinomas, lung adenomas, and hemangiomas. The majority of neoplastic lesions were seen in the liver. Males developed liver tumors with significantly greater incidence (75%) than female mice (28%), suggesting existence of a modifying effect of the sex hormone environment of the host on development of liver tumors initiated by administration of DMN to infant mice.

¹ This investigation was supported through Contract PH 43-65-67 from the National Cancer Institute, NIH, USPHS.

² Present address: Department of Radiology, University of Chicago, Chicago, Illinois 60637.

Received 4/19/68. Accepted 12/18/68.

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