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.
Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104.
P C
PC
Billings
J M
JM
Habres
A R
AR
Kennedy
D000818:Animals; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D010447:Peptide Hydrolases / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate
D009842:Oligopeptides; D011480:Protease Inhibitors; D010447:Peptide Hydrolases; D013755:Tetradecanoylphorbol Acetate