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

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Dimethylbenz(a)anthracene (DMBA) is a carcinogen that induces mammary tumors.
• Chromatin composition plays a role in tumor growth and regression.
• Prolactin is a hormone implicated in the development of mammary tumors.

Purpose of the Study:

• To compare the chemical composition of chromatin in growing and regressing DMBA-induced mammary tumors.
• To investigate the role of prolactin in the regression of these tumors.
• To elucidate the effects of 2-bromo-alpha-ergocryptine (CB-154) on tumor chromatin and DNA synthesis.

Main Methods:

• Induction of mammary tumors in rats using DMBA.
• Administration of CB-154 to induce tumor regression.
• Analysis of chromatin composition, including histone and nonhistone chromosomal proteins (NHCP) relative to DNA.
• Measurement of 3H-thymidine incorporation into DNA to assess synthesis.
• Varying doses of ovine prolactin were administered concurrently with CB-154.

Main Results:

• CB-154 treatment led to tumor regression in 70% of neoplasms, characterized by decreased DNA synthesis and increased NHCP/DNA ratio.
• Non-responsive tumors showed no significant changes in chromatin composition.
• Low-dose prolactin prevented CB-154's effects on DNA synthesis and chromatin.
• High-dose prolactin increased tumor DNA synthesis and counteracted CB-154's effects.

Conclusions:

• CB-154's effects on DMBA-induced mammary tumors are primarily mediated by prolactin secretion inhibition.
• Tumor regression following prolactin deprivation is associated with an elevated NHCP/DNA ratio.
• The study suggests a potential involvement of tumor cell membranes in the regression mechanism of prolactin-dependent mammary tumors.