Inhibition of radiation-induced transformation of C3H/10T1/2 cells by specific protease substrates.

In the current studies, we have examined the effect of two specific protease substrates, the thrombin substrate Boc-Val-Pro-Arg-MCA and the chymotrypsin substrate Suc-Ala-Ala-Pro-Phe-MCA, on the oncogenic transformation of C3H/10T1/2 cells induced with: (i) 6 Gy of X-radiation and (ii) 4 Gy of X-radiation followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Both substrates reduced radiation transformation while only Suc-Ala-Ala-Pro-Phe-MCA suppressed the TPA enhancement of radiation transformation. We have previously reported that C3H/10T1/2 cells contain at least two proteolytic activities which will cleave these substrates. Our results therefore suggest that: (i) these substrates may inhibit oncogenic transformation due to the fact that they are competitive substrates for these enzymes; and (ii) two or more proteases play an important role in the malignant transformation of these cells.