Abstract

Glucuronidation is a principal conjugation pathway in all vertebrate tissues, but is readily reversed by Beta-glucuronidase, also a ubiquitous enzyme. This pathway functions in the detoxification and excretion of several classes of xenobiotics, including carcinogens. The primary objective of this study is to establish the theory that reducing (inhibiting) Beta-glucuronidase activity during carcinogen exposure reduces tumor induction due to increase sequestering and excretion of carcinogens as the glucuronides. D-glucaro-1, 4-lactone is a potent endogenous inhibitor of Beta-glucuronidase. Specific objectives of this study are (i) to confirm the potent anticarcinogenic activity of 2,5-di-O-acetyl-D-glucaro-1, 4-6,3-dilactone as a slow release form of D-glucuro-1,4-lactone (ii) to identify means of metabolically altering endogenous levels of the glucarolactone (iii) to identify food sources rich in the glucarolactone or alternatively to determine whether food stuffs which depress cancer incidence are rich in glucarolactone. These studies will utilize established carcinogenic regimens in rodents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA038125-03
Application #
3176157
Study Section
(SSS)
Project Start
1984-08-01
Project End
1988-03-31
Budget Start
1986-08-01
Budget End
1988-03-31
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210

  Publications

Oredipe, O A; Barth, R F; Dwivedi, C et al. (1992) Dietary glucarate-mediated inhibition of initiation of diethylnitrosamine-induced hepatocarcinogenesis. Toxicology 74:209-22
Dwivedi, C; Heck, W J; Downie, A A et al. (1990) Effect of calcium glucarate on beta-glucuronidase activity and glucarate content of certain vegetables and fruits. Biochem Med Metab Biol 43:83-92
Dwivedi, C; Oredipe, O A; Barth, R F et al. (1989) Effects of the experimental chemopreventative agent, glucarate, on intestinal carcinogenesis in rats. Carcinogenesis 10:1539-41
Abou-Issa, H; Koolemans-Beynen, A; Minton, J P et al. (1989) Synergistic interaction between 13-cis-retinoic acid and glucarate: activity against rat mammary tumor induction and MCF-7 cells. Biochem Biophys Res Commun 163:1364-9
Dwivedi, C; Downie, A A; Webb, T E (1989) Modulation of chemically initiated and promoted skin tumorigenesis in CD-1 mice by dietary glucarate. J Environ Pathol Toxicol Oncol 9:253-9
Oredipe, O A; Barth, R F; Dwivedi, C et al. (1989) Chemopreventative activity of dietary glucarate on azoxymethane-induced altered hepatic foci in rats. Res Commun Chem Pathol Pharmacol 65:345-59
Abou-Issa, H M; Duruibe, V A; Minton, J P et al. (1988) Putative metabolites derived from dietary combinations of calcium glucarate and N-(4-hydroxyphenyl)retinamide act synergistically to inhibit the induction of rat mammary tumors by 7,12-dimethylbenz[a]anthracene. Proc Natl Acad Sci U S A 85:4181-4
Walaszek, Z; Hanausek-Walaszek, M; Webb, T E (1988) Repression by sustained-release beta-glucuronidase inhibitors of chemical carcinogen-mediated induction of a marker oncofetal protein in rodents. J Toxicol Environ Health 23:15-27
Dwivedi, C; Downie, A A; Webb, T E (1987) Net glucuronidation in different rat strains: importance of microsomal beta-glucuronidase. FASEB J 1:303-7
Walaszek, Z; Hanausek-Walaszek, M; Webb, T E (1986) Dietary glucarate-mediated reduction of sensitivity of murine strains to chemical carcinogenesis. Cancer Lett 33:25-32

Showing the most recent 10 out of 12 publications