Pyrene acts as a cocarcinogen with the carcinogens benzo [a] pyrene, ?-propiolactone and radiation in the induction of malignant transformation in cultured mouse fibroblasts; soybean extract containing the Bowman-Birk inhibitor acts as an anticarcinogen

Abstract

Pyrene was found to act as a cocarcinogen in the induction of transformation of cultured Balb/c3T3 cells by three different types of carcinogens: a direct acting chemical carcinogen, beta-propiolactone, a chemical carcinogen requiring metabolic activation, benzo[a]pyrene, and a physical carcinogen (60Co) gamma radiation. Since pyrene enhanced transformation in vitro by approximately the same amount for all the carcinogens tested, these results suggest that the carcinogenic action of pyrene is not related to carcinogen metabolism or uptake in vitro. An extract of soybeans containing the Bowman-Birk protease inhibitor was shown to reduce transformation induced by beta-propiolactone, benzo[a]pyrene and gamma-rays, both with and without the cocarcinogenic effect of pyrene, to background levels; the magnitude of the reduction in transformation by the protease inhibitor preparation was unrelated to the concentration of carcinogen. Neither the mechanism for the cocarcinogenic action of pyrene not the anticarcinogenic effect of the soybean extract is known, but several hypotheses are discussed.

Perspectives in cancer chemoprevention.

“…The third mechanism is suppression of errorprone DNA repair. Protease inhibitors depress error-prone repair in bacteria (76), and it has been suggested that they could prevent carcinogenesis by inhibiting an error-prone repair system activated by proteases that, in turn, are induced by tumor promoters (77 (Table 3). Inhibiters ofPolyamine Metabolism.…”

Development of the Bowman‐Birk inhibitor for oral cancer chemoprevention and analysis of neu immunohistochemical staining intensity with Bowman‐Birk inhibitor concentrate treatment

“…Bowman‐Birk Inhibitor and BBIC have a broad spectrum of anticarcinogenic activity. In vitro studies in both radiation‐induced and chemically induced carcinogenesis models have demonstrated inhibition of carcinogen‐induced transformation with BBI and BBIC 93,101,107,108 . In animal models studied, BBI and BBIC suppressed carcinogenesis in studies involving mice, rats, and hamsters.…”

A growth-regulated protease activity that is inhibited by the anticarcinogenic Bowman-Birk protease inhibitor.

“…While protease inhibitors have been shown to have strong anticarcinogenic activity in in vivo and in vitro cancer model systems (for examples, see refs. [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21], relatively little is known about the precise mechanism(s) by which these compounds exert their suppressive effects. We have hypothesized that protease inhibitors block carcinogenesis by inhibiting cellular enzymes involved in induction and/or expression of the transformed phenotype (22)(23)(24).…”

“…The anticarcinogenic activity of the soybean-derived Bowman-Birk protease inhibitor (BBI) has been extensively studied in our laboratory (6,8,13,17,(19)(20)(21). The BBI is an 8-kDa protein that effectively inhibits trypsin and chymotrypsin (25) as well as several other proteases (22,(24)(25)(26)(27).…”

“…BBI has been shown to suppress dimethylbenz [a]anthraceneinduced cheek pouch carcinogenesis when topically applied (15), 3-methylcholanthrene-induced lung tumorigenesis when injected (20), and dimethylhydrazine-induced colon and liver carcinogenesis in mice when present in the diet (8,17,19). The BBI has also been shown to suppress radiation-induced transformation of C3H/1OT/2 mouse embryo fibroblast cells at nanomolar concentrations (21) and to inhibit the transformation of BALB/3T3 cells induced by radiation or chemical carcinogens (benzo[a]pyrene and P-propiolactone) (6). We have shown that BBI as well as other anticarcinogenic protease inhibitors are internalized by C3H/10T1/2 cells (7,28,29).…”