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Effect of the Bowman-Birk Protease Inhibitor on the Expression of Oncogenes in the Irradiated Rat Colon¹

Experimental Radiation Oncology, Department of Radiology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157

In this study, we tested the influence of i.p. Bowman-Birk protease inhibitor (BBI) administration on oncogene expression in unirradiated and irradiated rat colonic mucosa. Total cellular RNA was collected from the colonic mucosa, and the levels of c-myc, c-fos, c-Ha-ras, c-EGFR, and c-actin mRNA were examined by standard dot and Northern blot analyses. The data demonstrate that BBI is capable of preventing radiation-induced overexpression of c-myc and c-fos without interfering with the constitutive expression of these 2 genes. It was also determined that BBI did not interfere with either radiation-induced overexpression of c-Ha-ras and c-EGFR or the constitutive expression of c-Ha-ras, c-EGFR, or c-actin. The data demonstrate that the anticarcinogenic BBI selectively inhibits the overexpression of c-myc and c-fos while not affecting crypt cell proliferation. These results suggest that a protease is involved in the pathway for enhanced c-myc and c-fos expression and that protease inhibitors such as BBI can interrupt this pathway.

¹ This research was supported in part by NIH Grant RR-05404 and funds from the Department of Radiology, Bowman Gray School of Medicine of Wake Forest University.

² To whom requests for reprints should be addressed, at Department of Radiology, Bowman Gray School of Medicine, Wake Forest University, Medical Center Boulevard, Winston-Salem, NC 27157.

Received 3/ 4/91. Accepted 6/18/91.

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