Enhancement of carcinogenesis by the natural anticarcinogen indole-3-carbinol

Bailey, George S.; Hendricks, Jerry D.; Shelton, Dennis W.

doi:10.1016/0378-8741(88)90261-9

Cited by 25 publications

(29 citation statements)

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“…In contrast, these agents have been effective in inhibiting carcinogenesis or DNA adduct formation by various carcinogens, including DMBA, aflatoxin B1, MEIQ, NNk and cigarette smoke. Second, I3C has proven to be a liver carcinogen, at least in rainbow trout (31). However, the extrapolation of hepatic carcinogenicity between species has been notoriously difficult.…”

Section: Discussionmentioning

confidence: 99%

Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and diindolylmethane (DIM) on chemically-induced mammary carcinogenesis: Is DIM a substitute for I3C?

Lubet¹,

Heckman²,

Flora³

et al. 2011

Oncol Rep

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Abstract. the abilities of 5,6-benzoflavone (5,6-BF, a synthetic flavonoid), indole-3-carbinol (I3C, a plant derived product) or diindolylmethane (DIM, a condensation product of I3C) to alter the induction of mammary cancers induced by the carcinogens 7,12-dimethylbenzanthracene (DMBA) or N-methyl-N-nitrosourea (MNU) were evaluated. Interestingly, the first two agents act as aryl hydrocarbon receptor (AhR) agonists, while DIM does not. The agents were initially examined for their ability to inhibit DMBA-induced mammary carcinogenesis. Agents were administered for 14 days starting 7 days prior to a single dose of the carcinogen. Evaluated over an extensive range of doses (165, 550 and 1650 ppm in the diet), 5,6-BF caused a dose-dependent decrease of mammary cancers. In addition, 5,6-BF at doses of 1650 and 165 ppm in the diet blocked the induction of DMBA-induced DNA adducts in the mammary gland by approximately 85% and 45%, respectively. In contrast, DIM (180 or 20 mg/kg BW/day) failed to block induction of DMBA tumors. The effect of these agents on the promotion/progression phase of carcinogenesis using the MNU mammary cancer model was also determined. 5,6-BF (1650 or 165 ppm in the diet), I3C (180 or 60 mg/kg BW/day administered by gavage), or DIM (180 or 60 mg/kg BW/day by gavage) were initiated 5 days after the administration of MNU, and continually thereafter. 5,6-BF decreased MNUinduced mammary tumor multiplicity by 40-60%. I3C reduced tumor multiplicity at the high dose, while DIM at either dose had minimal effects on tumor multiplicity. Thus, 5,6-BF and I3C were highly effective against initiation of DMBA-induced mammary carcinogenesis, and were also effective against MNU-induced tumors during the promotion/progression phase of carcinogenesis. In contrast, DIM had minimal effects in either model; arguing that administration of DIM is not analogous to administration of I3C.

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Section: Discussionmentioning

confidence: 99%

Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and diindolylmethane (DIM) on chemically-induced mammary carcinogenesis: Is DIM a substitute for I3C?

Lubet¹,

Heckman²,

Flora³

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…AFB1 hepatocarcinogenesis can be blocked in rats by co-treating animals with the antioxidant ethoxyquin (172) or the antischistosomal drug Oltipraz (173), apparently through induction of GST Yc2 with high specificity for AFB1-8,9-oxide. (34) and later confirmed in rats (174), that the candidate anticarcinogen indole-3-carbinol can behave as a potent tumor promoter under some exposure protocols has raised as yet unresolved safety concerns over its proposed use in human breast cancer chemoprevention.…”

Section: Tumor Promotion and Inhibition In Troutmentioning

confidence: 99%

Fish models for environmental carcinogenesis: the rainbow trout.

Bailey

Williams

Hendricks

1996

Environ Health Perspect

171

114

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Progress over the past 30 years has revealed many strengths of the rainbow trout as an alternative model for environmental carcinogenesis research. These include low rearing costs, an early life-stage ultrasensitive bioassay, sensitivity to many classes of carcinogen, a well-described tumor pathology, responsiveness to tumor promoters and inhibitors, and a mechanistically informative nonmammalian comparative status. Low-cost husbandry, for example, has permitted statistically challenging tumor study designs with up to 10,000 trout to investigate the quantitative interrelationships among carcinogen dose, anticarcinogen dose, DNA adduct formation, and final tumor outcome. The basic elements of the trout carcinogen bioassay include multiple exposure routes, carcinogen response, husbandry requirements, and pathology. The principal known neoplasms occur in liver (mixed hepatocellular/cholangiocellular adenoma and carcinoma, hepatocellular carcinoma), kidney (nephroblastoma), swim bladder (adenopapilloma), and stomach (adenopapilloma). Trout possess a complex but incompletely characterized array of cytochromes P450, transferases, and other enzymic systems for phase and phase 11 procarcinogen metabolism. In general, trout exhibit only limited capacity for DNA repair, especially for removal of bulky DNA adducts. This factor, together with a high capacity for P450 bioactivation and negligible glutathione transferase-mediated detoxication of the epoxide, accounts for the exceptional sensitivity of trout to aflatoxin B1 carcinogenesis. At the gene level, all trout tumors except nephroblastoma exhibit variable and often high incidences of oncogenic Ki-ras gene mutations. Mutations in the trout p53 tumor suppressor gene have yet to be described. There are many aspects of the trout model, especially the lack of complete organ homology, that limit its application as a surrogate for human cancer research. Within these limitations, however, it is apparent that trout and other fish models can serve as highly useful adjuncts to conventional rodent models in the study of environmental carcinogenesis and its modulation. For some problems, fish models can provide wholly unique approaches.Environ Health Perspect 104(Suppl 1): 5-21 (1996)

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“…Essentially, there is evidence that, not surrisingly, proto-oncogenes exist in fish, and presumably they can be activated by similar changes to those found in mamals. In contrast, the study of promoters in fish (Bailey et al 1987a(Bailey et al , 1987b(Bailey et al , 1988) is limited to a demonstration of the promotional effects of the PCB formulation…”

Section: Hepatocarcinogenesis In Fishmentioning

confidence: 99%

Vacuolation, proliferation and neoplasia in the liver of Boston Harbor winter flounder (Pseudopleuronectes americanus)

Moore¹

1991

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Enhancement of carcinogenesis by the natural anticarcinogen indole-3-carbinol

Cited by 25 publications

References 0 publications

Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and diindolylmethane (DIM) on chemically-induced mammary carcinogenesis: Is DIM a substitute for I3C?

Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and diindolylmethane (DIM) on chemically-induced mammary carcinogenesis: Is DIM a substitute for I3C?

Fish models for environmental carcinogenesis: the rainbow trout.

Vacuolation, proliferation and neoplasia in the liver of Boston Harbor winter flounder (Pseudopleuronectes americanus)

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