Changes in chromatin composition associated with hormone-dependent mammary tumor regression.

The chemical composition of chromatin from dimethylbenz(a)anthracene (DMBA)-induced mammary tumors was compared in growing and regressing neoplasms. Tumor regression was induced by 2-bromo-alpha-ergocryptine (CB-154) administration to the tumor-bearing rats. Seventy percent of the neoplasms showed a sharp fall in the levels of 3H-thymidine incorporation into DNA after 7-8 days of treatment (1 mg CB-154/day). These CB-154-responsive tumors showed a significant increase in nonhistone chromosomal proteins (NHCP) relative to DNA, while the histone fraction remained constant. Non-responsive tumors showed no change in their chromatin composition. Low doses of ovine prolactin (18 IU) given together with CB-154 (1 mg) were able to prevent the effects of the latter on both DNA synthesis and chromatin composition of DMBA- induced mammary tumors. High doses of hormone (40 IU) produced a two-fold increase in the tumors' DNA synthesis irrespective of the simultaneous administration of 1- or 2-mg doses of CB-154. This high dose of hormone was also able to prevent the effects of CB-154 on chromatin composition of the tumors. We conclude that the above effects of CB-154 are exerted mainly, if not exclusively, through the inhibition of prolactin secretion. On the other hand, the regression of these neoplasms after prolactin deprivation seems to be associated with an increase in the NHCP/DNA ratio. The possibility of an involvement of tumor cell membrane in the mechanism of regression of prolactin-dependent mammary tumors is discussed.