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Collagen Synthesis in Capsules Surrounding Dimethylbenzanthracene-induced Rat Breast Tumors and the Effect of Pretreatment with ß-Aminopropionitrile¹

Departments of Surgery [I. K. C., R. F. D.], Pathology [C. W. M.], and Physiology [R. J. W.], MCV/VCU Cancer Center [R. F. D.], Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298

Collagen synthesis is increased over three-fold in capsules surrounding dimethylbenzanthracene-induced rat breast tumors compared to the tumor parenchyma and over six-fold compared to normal breast connective tissue. Increased collagen synthesis is independent of the rate of tumor growth and final tumor size. Pretreatment of animals with ß-aminopropionitrile to inhibit collagen cross-linking caused an 82% decrease in tumor formation and a significant reduction in tumor volume (approximately 0.4 cu cm) compared to controls (approximately 10 cu cm). The four small tumors that did develop in the lathyritic animals had increased collagen synthesis in the interior tumor stroma and reduced collagen synthesis in the tumor capsule. These findings suggest that the collagenous capsule surrounding dimethylbenzanthracene tumors functions as a physical barrier to protect the tumor from the immune system of the host. The apparent antitumor effects of ß-aminopropionitrile may be due to immunopotentiation and/or cytotoxic actions of the drug.

¹ This investigation was supported by Grant CA17297, awarded by the National Cancer Institute, Department of Health, Education, and Welfare. A preliminary report of a portion of this work was presented (4).

² To whom requests for reprints should be addressed, at Box 756, Medical College of Virginia, Richmond, Va. 23298.

Received 1/15/79. Accepted 4/24/79.