Animal studies addressing the carcinogenicity of TCDD (or related compounds) with an emphasis on tumour promotion

  title={Animal studies addressing the carcinogenicity of TCDD (or related compounds) with an emphasis on tumour promotion},
  author={Yvonne P. Dragan and Dieter Schrenk},
  journal={Food Additives \& Contaminants},
  pages={289 - 302}
Dioxin and certain structurally related compounds increase the incidence of liver neoplasms in rodents upon chronic bioassay. Short-term studies indicate the lack of direct DNA-damaging effects including covalent binding to DNA; however, secondary mechanisms may be important in the observed carcinogenicity as these chemicals affect a number of pathways necessary for maintenance of normal growth control and differentiation status. Studies with TCDD in the mouse skin support a lack of initiating… 

Mode of action and dose–response framework analysis for receptor-mediated toxicity: The aryl hydrocarbon receptor as a case study

An expert panel was convened as part of a workshop on receptor-mediated liver tumorigenicity and proposed a MOA beginning with sustained AHR activation, eventually leading to liver tumors via a number of other processes, including increased cell proliferation of previously initiated altered hepatic foci, inhibition of intrafocal apoptosis and proliferation of oval cells.

Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology

  • P. Mandal
  • Biology, Chemistry
    Journal of Comparative Physiology B
  • 2005
TCDD induces a broad spectrum of biological responses, including induction of cytochrome P-450 1A1 (CYP1A1), disruption of normal hormone signaling pathways, reproductive and developmental defects, immunotoxicity, liver damage, wasting syndrome, and cancer.

Carcinogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in experimental models.

A better understanding of the mechanisms of the carcinogenicity of TCDD is mandatory to provide a rational basis for a better inter-species extrapolation, and a more reliable risk assessment for the carcinogenic potency of the class of dioxinlike contaminants in humans.

The Comparative Immunotoxicity of Five Selected Compounds Following Developmental or Adult Exposure

It is demonstrated that functional immaturity alone predisposes the young to infection, and the developing immune system was found to be at greater risk than that of the adult, either because lower doses produced immunotoxicity, adverse effects were more persistent, or both.

Carcinogenic Food Contaminants

  • C. Abnet
  • Medicine
    Cancer investigation
  • 2007
A summary of the evidence for the carcinogenicity of food contaminants and other agents and the ranks provided by two important assessment programs are presented.

TCDD affects DNA double strand-break repair.

It is demonstrated that TCDD, potentially acting via the AhR, can modulate HR repair of DNA DSBs in CHO 33 cells.



Toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD).

The most recent research indicates that the biologic uptake and toxicity of TCDD may be significantly decreased if theTCDD is adsorbed onto carbon or soil particles, which is helpful in hazard assessment of exposure to T CDD.

Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: histologic, biochemical, and cell proliferation endpoints.

It is demonstrated that dose-response relationships for TCDD's effects on cell proliferation growth of altered hepatic foci are different from previously reported effects on P450 gene expression, indicating that different biological or biochemical responses may exhibit different dose- response relationships.

A method to quantitate the relative initiating and promoting potencies of hepatocarcinogenic agents in their dose-response relationships to altered hepatic foci.

Based on quantitative stereologic calculations, parameters for the estimation for the relative potency of chemicals as initiating or promoting agents have been established and may be useful as quantitative estimates of the potency of hepatocarcinogenic agents.

Promotion of N-nitrosodimethylamine-initiated mouse lung tumors following single or multiple low dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Data demonstrate the potent tumor promoting capability of TCDD in mouse lung and indicates that NDMA may have been toxic to the lungs of NDMA-treated mice, as evidenced by the infiltration of pigmented macrophages.

Promotion of spontaneous preneoplastic cells in rat liver as a possible explanation of tumor production by nonmutagenic compounds.

Cells in the spontaneous foci appear to possess a defect in growth control, rendering them more susceptible to endogenous and exogenous growth stimuli, and long-term bioassay for carcinogenicity will not discriminate between initiating and promoting compounds if preneoplastic lesions develop in control animals.

Lack of tumor-promoting ability of certain environmental chemicals in a two-stage mouse skin tumorigenesis assay.

Results indicate that dosage may be an important factor in promotion, since several of the tested compounds are known to be promoters in pulmonary and hepatic systems.

Persistence of TCDD-induced hepatic cell proliferation and growth of enzyme altered foci after chronic exposure followed by cessation of treatment in DEN initiated female rats.

It is concluded that as opposed to CYP1A1 induction the more complex biological responses, cell proliferation and selective growth of certain preneoplastic foci, are persistent after prolonged TCDD treatment within the experimental framework of this study.

Characterization of the promotion of altered hepatic foci by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the female rat.

C cessation of exposure to TCDD after a brief duration led to a reversal of its promotional effects on the majority of AHF, while prolonged exposure led to maintained promotion of a minority ofAHF.