Dose-response and potential thresholds in tumour development.

ECNIS is a Network of Excellence within the European Union’s Sixth Framework Programme, Priority 5: Food Quality and Safety. It brings together some of the best European research groups in a concerted effort to achieve improved understanding of the environmental causes of cancer, of the potential of diet to prevent cancer, and of the ways by which heredity can affect individual susceptibility to carcinogens, with the ultimate aim of reducing the cancer burden in Europe. ECNIS is coordinated by Prof. Konrad Rydzynski, The Nofer Institute of Occupational Medicine, Sw. Teresy 8, 91-348 ¸Lodz, Poland. This review has been prepared as part of ECNIS Work Package 10: Mechanistic research to support cancer hazard and risk assessment.

[1]  M E Andersen,et al.  Mechanistic modeling of rodent liver tumor promotion at low levels of exposure: an example related to dose-response relationships for 2,3,7,8-tetrachlorodibenzo-p-dioxin , 1998, Human & experimental toxicology.

[2]  Abraham Nyska,et al.  Dose-Additive Carcinogenicity of a Defined Mixture of “Dioxin-like Compounds” , 2004, Environmental health perspectives.

[3]  G. Clark,et al.  Dose response for TCDD promotion of hepatocarcinogenesis in rats initiated with DEN: histologic, biochemical, and cell proliferation endpoints. , 1993, Environmental health perspectives.

[4]  M E Andersen,et al.  Hepatic foci in rats after diethylnitrosamine initiation and 2,3,7,8-tetrachlorodibenzo-p-dioxin promotion: evaluation of a quantitative two-cell model and of CYP 1A1/1A2 as a dosimeter. , 1997, Toxicology and applied pharmacology.

[5]  H M Bolt,et al.  Challenging dogma: thresholds for genotoxic carcinogens? The case of vinyl acetate. , 2003, Annual review of pharmacology and toxicology.

[6]  S. Fukushima,et al.  Hormesis and dose-response-mediated mechanisms in carcinogenesis: evidence for a threshold in carcinogenicity of non-genotoxic carcinogens. , 2005, Carcinogenesis.

[7]  M. Schwarz,et al.  Carcinogenic risks of dioxin: mechanistic considerations. , 2005, Regulatory toxicology and pharmacology : RTP.

[8]  G. Clark,et al.  Ovarian hormones enhance 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated increases in cell proliferation and preneoplastic foci in a two-stage model for rat hepatocarcinogenesis. , 1991, Cancer research.

[9]  G. Lucier,et al.  Differences in kinetics of induction and reversibility of TCDD-induced changes in cell proliferation and CYP1A1 expression in female Sprague-Dawley rat liver. , 1998, Carcinogenesis.

[10]  T. Mikami,et al.  Comparison of the mutational spectra of the lacZ transgene in four organs of the MutaMouse treated with benzo[a]pyrene: target organ specificity. , 2000, Mutation research.

[11]  G. Jenkins,et al.  Do dose response thresholds exist for genotoxic alkylating agents? , 2005, Mutagenesis.

[12]  T. Fox,et al.  Gene expression and cell proliferation in rat liver after 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure. , 1993, Cancer research.

[13]  F. Oesch,et al.  Metabolic Detoxification: Implications for Thresholds , 2000, Toxicologic pathology.

[14]  F. Oesch,et al.  2,3,7,8-tetrachlorodibenzo-p-dioxin-dependent release from contact inhibition in WB-F344 cells: involvement of cyclin A. , 2002, Toxicology and applied pharmacology.

[15]  L Edler,et al.  Modeling the number and size of hepatic focal lesions following exposure to 2,3,7,8-TCDD. , 1996, Toxicology and applied pharmacology.

[16]  Muller Jja,et al.  Tumorigenic effects in Wistar rats orally administered benzo[a] pyrene for two years (gavage studies). Implications for human cancer risks associated with oral exposure to polycyclic aromatic hydrocarbons , 2002 .

[17]  C. Weiss,et al.  Complementation of Ah receptor deficiency in hepatoma cells: negative feedback regulation and cell cycle control by the Ah receptor. , 1996, Experimental cell research.

[18]  A. Koff,et al.  p27Kip1 induction and inhibition of proliferation by the intracellular Ah receptor in developing thymus and hepatoma cells , 1999 .

[19]  M. Yamada,et al.  Semi-quantitative evaluation of genotoxic activity of chemical substances and evidence for a biological threshold of genotoxic activity. , 2000, Mutation research.

[20]  A. Buchmann,et al.  Inhibition of apoptosis during 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated tumour promotion in rat liver. , 1995, Carcinogenesis.

[21]  C. Wade,et al.  Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. , 1978, Toxicology and applied pharmacology.

[22]  T. Tsukamoto,et al.  Lack of initiation activity in rat liver of low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline. , 2003, Cancer letters.

[23]  Y. Dragan,et al.  Quantitative analysis of dose- and time-dependent promotion of four phenotypes of altered hepatic foci by 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Sprague-Dawley rats. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[24]  S. J. Culp,et al.  DNA Adduct Measurements in Relation to Small Intestine and Forestomach Tumor Incidence during the Chronic Feeding of Coal TAR or Benzo[A]Pyrene to Mice , 1996 .

[25]  G L Kimmel,et al.  Developmental and reproductive toxicity of dioxins and related compounds: cross-species comparisons. , 1993, Critical reviews in toxicology.

[26]  D W Gaylor,et al.  A comparison of the tumors induced by coal tar and benzo[a]pyrene in a 2-year bioassay. , 1998, Carcinogenesis.

[27]  M. DeVito,et al.  Dose-response relationships in mice following subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: CYP1A1, CYP1A2, estrogen receptor, and protein tyrosine phosphorylation. , 1994, Toxicology and applied pharmacology.

[28]  T. Tsukamoto,et al.  Lack of a Dose‐response Relationship for Carcinogenicity in the Rat Liver with Low Doses of 2‐Amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline or N‐Nitrosodiethylamine , 2002, Japanese journal of cancer research : Gann.

[29]  R. Conolly,et al.  Nonmonotonic dose-response relationships: mechanistic basis, kinetic modeling, and implications for risk assessment. , 2004, Toxicological sciences : an official journal of the Society of Toxicology.