Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 12, 2001
Publication Date: N/A
Interpretive Summary: We previously demonstrated that diets containing soy protein isolate or whey protein reduce the incidence of breast tumors in rats. This study focuses on the mechanisms by which these proteins may act. The data show that soy and whey act to reduce that conversion of potential carcinogens (procarcinogens) to active carcinogens. This has the ultimate effect of reducing the numbers of tumors formed from exposure to procarcinogens. The study also examined the mechanisms by which soy or whey were able to produce these effects and found that each probably has a unique action and studies are currently underway to delineate these mechanisms further.
Technical Abstract: One possible mechanism by which diet may reduce cancer risk is through enhancement of metabolic systems that prevent activation of carcinogens or accelerate carcinogen inactivation. We studied the effects of diet and 7/12-dimethylbenz-(a)anthracene (DMBA) on hepatic and mammary gland CYP1A1, CYP1A2 and CYP1B1enzymes in female Sprague-Dawley rats. Diets (AIN-93G) were fed from conception to adulthood, and DMBA was given by oral gavage at age 48-50 d. The protein sources of diets were casein (CAS), soy protein isolate (SPI) or whey protein hydrolysate (WPH). The DMBA-induced hepatic ethoxyresorufin-O-deethylase and methoxyresorufin-O-demethylase activities and CYP1A1 protein and mRNA expression were lower (P<0.05) in SPI-fed rats compared with those fed casein. Differences in mammary gland CYP1 expression were also observed with decreased DMBA induction (P<0.05) of all three CYP1 proteins and mRNAs in rats fed either SPI or WPHcompared with those fed CAS. Most notable were the decreased constitutive and DMBA-induced mammary gland expression of CYP1B1 protein of 93 and 96%, respectively, in the SPI-fed rats relative to the CAS-fed controls. The diet-induced changes in CYP1 enzyme expression were consistent with changes in the AhR and ARNT transcription factors that regulate them. Decreased (P<0.05) mammary constitutive AhR and ARNT proteins were measured in SPI-fed rats. There was also a 100% increase in constitutive AhR protein in the WPH-fed rats that paralleled a 100% increase in constitutive CYP1B1 protein in the mammary gland. These results demonstrate the importance of diet in regulation of phase 1 metabolism in liver and mammary gland, and suggest a potential mechanism by which soy or whey proteins reduce DMBA-induced mammary tumor incidence.