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Hormonal Treatment of Mammary Tumors in Rats Induced by 3-Methylcholanthrene (NSC-21970) and 7,12-Dimethylbenz(a)Anthracene (NSC-408823)¹

Mammary tumors induced in female rats by repeated gastric instillations of 3-methylcholanthrene grow more rapidly than tumors induced by single gastric instillations of 7,12-dimethylbenz (a) anthracene. Over a 6-week period, the inhibition of tumor growth by ovariectomy or by estradiol benzoate is more evident by inhibition of tumor weight of the MCA tumors, but complete regressions occur more frequently with DMBA tumors.

Mammary tumors appearing in female rats after administration of carcinogenic polycyclic hydrocarbons are used for the evaluation of cancer chemotherapeutic agents. The tumors are partially hormonedependent and in other ways are considered to resemble mammary carcinoma in humans.

Two experimental systems have been most popular. The 1st uses female Wistar rats that receive repeated gastric instillations of 3-methylcholanthrene (MCA), a method introduced by Shay and his coworkers (8) in 1949. The 2d system uses female Sprague-Dawley rats that are given single doses of 7,12-dimethylbenz(a)anthracene (DMBA), the method introduced by Huggins et al. (7) in 1961.

Few studies have compared systematically the appearance and behavior of mammary tumors induced by these 2 methods. We have reported one such study (6), and showed that the Sprague-Dawley rat is more susceptible than the Wistar rat to the induction of mammary tumors after gastric instillations of both carcinogens, as expressed in a greater proportion of animals that develop tumors, shorter mean time of appearance of such tumors, and a greater number of tumors per rat. These data are summarized in Table 1.

The same study (6) also revealed that the mammary tumors induced by repeated administrations of MCA grew significantly more rapidly than the tumors induced by single doses of DMBA, as expressed by the mean diameter of the masses on Day 30. There was no difference in growth in the 2 strains of rats. These data, recalculated as the mean volume of tumor per rat 21 days after appearance, are given in Table 2.

Tumors induced by multiple administrations of MCA in Wistar rats have been used in this laboratory in a series of studies that tested over 100 hormonal and nonhormonal chemicals (1,2,4,5). Tumors induced by single doses of DMBA in Sprague-Dawley rats have been used in similar investigations by Griswold et al. (3) and Teller et al. (9). We (4) suggested that the difference in the growth rate, as well as the difference in the effect of MCA and DMBA on the hormonal status of the host, could affect the therapeutic response (4). A direct comparison of the response of MCA- and DMBA-induced tumors to several chemotherapeutic agents appeared desirable, and such an experiment was started.

This report compares the growth of mammary tumors in female Wistar and Sprague-Dawley rats that received MCA or DMBA, and the response of such tumors to ovariectomy, estradiol benzoate (NSC-9566) and dromostanolone propionate (NSC-12198).³

¹ Supported by contract SA-43-ph-4344 from the Cancer Chemotherapy National Service Center, National Cancer Institute, USPHS.

³ NSC-9566: estradiol, 3-benzoate.

NSC-12198: 5-androstan-3-one, 17ß-hydroxy-2-methyl-, propionate.

² Fels Research Institute, Temple University School of Medicine, Philadelphia, Pennsylvania.