Acute effects of the Bowman-Birk protease inhibitor in mice.
The soybean-derived Bowman-Birk inhibitor (BBI) has been shown to inhibit carcinogenesis in both in vitro and in vivo model systems. In the present study, protease enzyme activity in selected tissues of male strain A mice was measured by hydrolysis of the synthetic substrate Boc-Val-Pro-Arg-MCA (t-butoxycarbornylvalylprolylarginine 7-amido-4-methylcoumarin). When added to homogenates of lung, liver and kidney in vitro, purified BBI inhibited hydrolytic activity at concentrations ranging from 10-100 microM. In vivo, hydrolytic activity was found to be significantly and in a dose-dependent manner, decreased in the lung as early as 2 h after i.p. injection of purified BBI. Less inhibition was found in the liver and kidney after in vivo administration of purified BBI. A crude preparation of BBI, given at 100 mg/kg, had no influence on the overall disposition of radiolabeled benzo[alpha]pyrene in mice although it decreased the hepatic activities of cytochrome P-450, 7-ethoxycoumarin-O-deethylase and ethoxy resorufin-O-deethylase. It is concluded that the chemopreventive effects of BBI on mouse lung tumor development are most likely mediated through its protease-inhibitory properties in the target organ rather than by a non-specific effect on metabolism and disposition of carcinogens.
Oreffo
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Toxic Substances Research and Teaching Program, University of California, Davis 95616.
Billings
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PC
Kennedy
A R
AR
Witschi
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H
D000595:Amino Acid Sequence; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000493:pharmacokinetics; D002273:Carcinogens / Q000378:metabolism / Q000493:pharmacokinetics; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D003374:Coumarins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology*
D002273:Carcinogens; D003374:Coumarins; D009842:Oligopeptides; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D001564:Benzo(a)pyrene; C036903:tertiary-butyloxycarbonyl-valyl-prolyl-arginyl-7-amino-4-methylcoumarin; D002918:Chymotrypsin