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The Effects of 7,12-Dimethylbenz(a)anthracene on the Ovarian Response of Mice and Rats to Gonadotrophins¹

Cancer Research Centre, University of British Columbia, Vancouver, Canada, and the National Cancer Institute of Canada, Toronto, Canada

Administration by stomach tube of 7,12-dimethylbenz(a)anthracene (DMBA) (30 mg/100 gm body weight) in oil caused a decrease in the ovarian weights of C57BL/6J, C3D2F₁, CAF₁, B6AF₁, B6D2F₁, and C57BL/6J x C3HeB/FeJ mice, but it did not affect the ovarian weights of C3HeB/FeJ x NZY mice or of Sprague-Dawley or Fischer rats.

DMBA treatment also eliminated the ovarian weight gain, which normally is seen 48 hours after chorionic gonadotrophin (CG) injection, in C57 mice 34 days of age or less, but there was no significant effect on the action of CG in stimulating ovarian weight gain in C57 mice 56 days of age or more. In C3D2F₁ mice, the ovarian weight response was eliminated up to 23 days of age, but in older mice of this strain the inhibition was not complete and was more variable in degree.

The ovarian weight response to CG was reduced within 3 days of DMBA treatment in mature B6D2F₁ or immature B6AF₁ mice, and within 7 days in mature CAF₁ mice. However, the carcinogen had no significant effect on ovarian weight stimulation by CG in mature B6AF₁, C57BL/6J x C3HeB/FeJ, or C3HeB/FeJ x NZY mice.

In a less extensive series of experiments, substitution of pregnant mare serum (PMS) as the gonadotrophin after DMBA treatment gave results parallel to those obtained with CG. Ovarian weight gain following PMS was inhibited in immature Sprague-Dawley rats, but not in Fischer rats at any of the 3 weights studied.

Uterine weight was lower in most DMBA-treated immature mice and Sprague-Dawley rats than in the controls and increased less following gonadotrophin injection. In the majority of mature mice and rats, however, uterine weights did not differ significantly between DMBA-treated and control animals either before or after gonadotrophin injection.

Amounts of DMBA in arachis oil equivalent to or less than 20 mg/100 gm administered through a stomach tube or 2 mg/100 gm injected intraperitoneally were ineffective in inhibiting the action of gonadotrophins on the ovaries of immature C57BL/6J mice.

The number of viable ovarian follicles was greatly reduced in mice within 3 days after DMBA treatment, and there were none present 100 days afterwards. There was no obvious toxic effect of DMBA on the rat ovaries.

Carcinogen treatment was followed by a loss of total body weight in some, but not all, rats and mice. There was no absolute correlation between the inhibition of ovarian response to gonadotrophin and the decrease in total body weight following treatment with the carcinogen.

An interpretation of the results is given in terms of the action of DMBA on pituitary secretion in both mice and rats, and in terms of direct action on ovarian follicles in mice only.

¹ This study was supported by the National Cancer Institute of Canada, Toronto, Canada.

Received 9/ 9/68. Accepted 2/21/69.

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