Dietary glucarate-mediated reduction of sensitivity of murine strains to chemical carcinogenesis

Wałaszek, Zbigniew; Hanausek-Walaszek, Malgorzata; Webb, Thomas E.

doi:10.1016/0304-3835(86)90098-4

Cited by 26 publications

(7 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, we show that both glucuronic acid and D-saccharic acid 1,4 lactone are strong inhibitors of b-glucuronidase activity at concentrations 1.0, 2.0, 4.0 mM. These data agreed with those of Walaszek et al (1986) and Dutton et al (1988) who indicated that D-saccharic acid 1,4 lactone is a well-known natural inhibitor of both human and E. coli b-glucuronidase enzyme activities. Also, D-saccharic acid 1,4 lactone was found to inhibit bglucuronidase enzyme activity in transgenic tobacco (Hodal et al 1992).…”

Section: Discussionsupporting

confidence: 94%

Characterization of inhibitor(s) of β-glucuronidase enzyme activity in GUS-transgenic wheat

Ramadan

Eissa

El-Domyati

et al. 2011

Plant Cell Tiss Organ Cult

View full text Add to dashboard Cite

The uidA gene, encoding for b-glucuronidase (GUS), is the most frequently used reporter gene in plants.As a reporter enzyme, GUS can be assayed both qualitatively and quantitatively. In wheat, there are numerous reports of failure in detecting GUS enzyme activity in tissues of transgenic plants, while other reports have suggested presence of b-glucuronidase inhibitor(s) in wheat tissues. In the present study, we show that the b-glucuronidase enzyme activity is not only tissue-specific but also genotype-dependent. Our data demonstrate that the glucuronic acid could be the candidate inhibitor for b-glucuronidase enzyme activity in wheat leaves and roots. It should be noted that the assays to detect b-glucuronidase enzyme activity in wheat should be interpreted carefully. Based on the data of our present study, we recommend studying the chemical pathways, the unintended effects and the possible loss-of-function of any candidate transgene prior to transformation experiments.

show abstract

Section: Discussionsupporting

confidence: 94%

Characterization of inhibitor(s) of β-glucuronidase enzyme activity in GUS-transgenic wheat

Ramadan

Eissa

El-Domyati

et al. 2011

Plant Cell Tiss Organ Cult

View full text Add to dashboard Cite

show abstract

“…According to one proposed mechanism, plant intake may raise levels of circulating D-glucaric acid, a plant constituent and potential β-glucuronidase inhibitor. D-glucaric acid has been shown to significantly reduce chemical carcinogen-mediated mammary, liver, and skin tumors in experimental animal models (12-16). D-glucaric acid is converted into D-glucaro-1,4-lactone, a potent inhibitor of β-glucuronidase (17, 18), particularly microsomal β-glucuronidase (19), although other chemoprotective mechanisms have been proposed.…”

Section: Introductionmentioning

confidence: 99%

Dietary and Demographic Correlates of Serum β-Glucuronidase Activity

Maruti

Chang

et al. 2010

Nutrition and Cancer

View full text Add to dashboard Cite

show abstract

“…Since CGT undergoes a slow partial conversion in the stomach to the potent B-glucuronidase inhibitor D-glucaro-1,4-lactone (12)(13)(14)(15), it is possible that CGT enhances the net glucuronidation of HPR, as was shown for bilirubin (15). Therefore, through enhancement of glucuronidation, CGT may cause longer retention of HPR in extrahepatic tissues, in general, and the mammary gland of the female rat, in particular.…”

Section: Me2bmentioning

confidence: 98%

“…This activity is believed to derive from the slow conversion of approximately one-third of the CGT to the potent f3-glucuronidase inhibitor D-glucaro-1,4-lactone, at the acid pH of the stomach. The increased net glucuronidation could theoretically lead to increased excretion of carcinogens and promoting agents, including steroid hormones, as glucuronide conjugates (12)(13)(14). Consequently, CGT has been observed to inhibit the initiation and promotion phases of tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

“…Studies from this laboratory have shown that dietary calcium glucarate (CGT) is an effective preventative chemical (chemopreventative) agent against cancer induction in several rodent organs, including the mammary gland (12,13). This activity is believed to derive from the slow conversion of approximately one-third of the CGT to the potent f3-glucuronidase inhibitor D-glucaro-1,4-lactone, at the acid pH of the stomach.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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.

Abou-Issa

Duruibe²,

Minton³

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Calcium glucarate and N-(4-hydroxyphenyl)-retinamide were evaluated individually and in combination in the diet as preventative chemical agents, by using the induction of rat mammary tumors by 7,12-dimethylbenz[alanthracene as the test system. When tested separately over 18 weeks, optimal doses of calcium glucarate (128 mmol/kg of diet) or N-(4-hydroxyphenyl)retinamide (1.5 mmol/kg of diet) administered daily inhibited tumor incidence by 50% or 57% and tumor multiplicity by 50% or 65%, respectively. Suboptimal doses of calcium glucarate (32 mmol/kg) and of N-(4-hydroxyphenyl)-retinamide (0.75 mmol/kg) inhibited tumor incidence by 15% and 5% but had no inhibitory effect on tumor multiplicity. In contrast, the combination of calcium glucarate (32 mmol/kg) and N-(4-hydroxyphenyl)retinamide (0.75 mmol/kg) inhibited tumor incidence and tumor multiplicity by 50%. Similar synergism was observed with the combination of calcium glucarate (64 mmol/kg) and N-(4-hydroxyphenyl)retinamide (0.75 mmol/kg), the inhibition being 55460%. HPLC Retinoids have also been shown to inhibit the neoplastic transformation of mammary tissue by carcinogenic hydrocarbons in whole-organ culture (7). The inhibition of carcinogen-induced tumors by HPR has been confirmed and the mechanisms underlying this inhibition have been investigated (8). The effect of limiting feeding of retinoids to specific time periods of the carcinogenic process has also been reported (7,9). Although retinyl acetate tends to accumulate in the liver resulting in mild hepatotoxicity, HPR does not have this disadvantage (5). A comprehensive study has been made of HPR metabolism in the rat (10). The overwhelming evidence suggests that retinoids are inhibitory to the initiation and promotion phases of rat mammary carcinogenesis (11).Studies from this laboratory have shown that dietary calcium glucarate (CGT) is an effective preventative chemical (chemopreventative) agent against cancer induction in several rodent organs, including the mammary gland (12, 13). This activity is believed to derive from the slow conversion of approximately one-third of the CGT to the potent f3-glucuronidase inhibitor D-glucaro-1,4-lactone, at the acid pH of the stomach. The increased net glucuronidation could theoretically lead to increased excretion of carcinogens and promoting agents, including steroid hormones, as glucuronide conjugates (12)(13)(14). Consequently, CGT has been observed to inhibit the initiation and promotion phases of tumorigenesis.The The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. §1734 solely to indicate this fact.

show abstract

Dietary glucarate-mediated reduction of sensitivity of murine strains to chemical carcinogenesis

Cited by 26 publications

References 17 publications

Characterization of inhibitor(s) of β-glucuronidase enzyme activity in GUS-transgenic wheat

Characterization of inhibitor(s) of β-glucuronidase enzyme activity in GUS-transgenic wheat

Dietary and Demographic Correlates of Serum β-Glucuronidase Activity

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.

Contact Info

Product

Resources

About