Chapter 9: Genotoxicity and Carcinogenicity

IEH (2002). Assessment of Chemical Carcinogens: Background to General Principles of a Weight of Evidence Approach. 17 pp. Leicester, UK: Medical Research Council. Web site: http://www.le.ac.uk/ieh/ (Accessed 1.6.02)

Fielder R.J. , Atterwill C.K. , Anderson D. , Boobis A.R. , Botham P. , Chamberlain M. , Combes R. , Duffy P. , Lewis R.W. , Lumley C.E. , Kimber I. , & Newall D.R. (1997). BTS working party report on in vitro toxicology. Human and Experimental Toxicology 16, S1–S40.

DOH (Department of Health) (2000). Report on Health and Social Subjects, Guidelines for the Testing of Chemicals for Mutagenicity. Committee on Mutagenicity of Chemicals in Food, Consumer Products and the Environment. London, UK: HMSO.

DOH (Department of Health) (1989). Guidelines for the Testing of Chemicals for Mutagenicity. London: HMSO.

Combes R.D. (1995). Regulatory genotoxicity testing: a critical appraisal. ATLA 23, 352–379.

Mitchell I. deG. , & Combes R.D. (1996). In vitro genotoxicity and cell transformation assessment. In In Vitro Methods in Pharmaceutical Research (ed. Castell J.V. , & Gómez-Lechón M.J. ), pp. 317–352. London, UK: Academic Press.

ICH (1997). Report of Fourth International Conference on Harmonisation, Brussels, July, 1997, Genotoxicity: Standard Battery of Tests. Step 4 Report. Geneva, Switzerland: ICH.

Combes R.D. (1999). Mutagenicity. In Cosmetics: Controlled Efficacy Studies and Regulation (ed. Elsner P. , Merk H. , & Mailbach H.I. ), pp. 291–308. New York, NY, USA: Springer-Verlag.

Zeiger E. (2001). Genetic toxicity tests for predicting carcinogenicity. In Genetic Toxicology and Cancer Risk Assessment (ed. Choy W.N. ), pp. 29–46. New York, NY, USA: Marcel Dekker.

Combes R.D. (1992). The in vivo relevance of in vitro genotoxicity assays incorporating enzyme activation systems. In Progress in Drug Metabolism, Vol. 13 (ed. Gibson C.G. ), pp. 295–321. London, UK: Taylor & Francis.

Macé K. , Offord E.A. , & Pfeifer A.M.A. (1997). Drug metabolism and carcinogen activation studies with human genetically engineered cells. In In Vitro Methods in Pharmaceutical Research (ed. Castell J.V. , & Gómez-Lechón M.J. ), pp. 433–456. London, UK: Academic Press.

Wiebel F.J. , Andersson T.B. , Casciano D.A. , Dickins M. , Fischer V. , Glatt H. , Horbach J. , Langenbach R.J. , Luyten W. , Turchi G. , & Vandewalle A. (1997). Genetically engineered cell lines: characterisation and applications in toxicity testing. ATLA 25, 625–639.

Crespi C. (1995). Use of genetically engineered cells for genotoxicity testing. In Environmental Mutagenesis (ed. Phillips D.H. , & Venitt S. ), pp. 233–260. Oxford, UK: S.Bios Scientific Publishers.

Kirsch-Volders M. , Sofuni T. , Aardema M. , Albertini S. , Eastmond D. , Fenech M. , Ishidate M. Jr. , Lorge E. , Norppa H. , Surralles J. , von der Hude W. , & Wakata A. (2000). Report from the In Vitro Micronucleus Assay Working Group. Environmental and Molecular Mutagenesis 35, 167–172.

Stopper H. , & Müller S.O. (1997). Micronuclei as a biological endpoint for genotoxicity: a minireview. Toxicology in Vitro 11, 661–667.

Aardema M.J. , & Kirsch-Volders M. (2001). The in vitro micronucleus assay. In Genetic Toxicology and Cancer Risk Assessment (ed. Choy W.N. ), pp. 163–186. New York, NY, USA: Marcel Dekker.

Combes R.D. (1997). Detection of nongenotoxic carcinogens: major barriers to replacement of the rodent bioassay. In Animal Alternatives, Welfare and Ethics. (ed. van Zutphen L.F.M. , & Balls M. ), pp. 627–634. Amsterdam, The Netherlands: Elsevier.

Gottmann E. , Kramer S. , Pfahringer B. , & Helma C. (2001). Data quality in predictive toxicology: reproducibility of rodent carcinogenicity experiments. Environmental Health Perspectives 109, 509–514.

Ashby J. , & Tennant R.W. (1991). Definitive relationships among chemical structure, carcinogenicity and mutagenicity of 301 chemicals tested by the US NTP. Mutation Research 257, 229–306.

Choy W.N. (2001). Genotoxic and nongenotoxic mechanisms of carcinogenesis. In Genetic Toxicology and Cancer Risk Assessment (ed. Choy W.N. ), pp. 47–72. New York, NY, USA: Marcel Dekker.

Combes R.D. (2000). The use of structure–activity relationships and markers of cell toxicity to detect nongenotoxic carcinogens. Toxicology in Vitro 14, 387–399.

D'Arcy P.F. , & Harron D.W.G. (1997). Proceedings of the Fourth International Conference on Harmonisation, Brussels, 1997. Belfast, UK: Queen's University.

Tennant R.W. , Stasiewicz S. , Mennear J. , French J.E. , & Spalding J.W. (1999). Genetically altered mouse models for identifying carcinogens. In IARC Scientific Publications No. 146: The Use of Short-and Medium-Term Tests for Carcinogens and Data on Genetic Effects in Carcinogenic Hazard Evaluation (ed. McGregor D.B. , Rice J.M. , & Venitt S. ), pp. 123–150. Lyon, France: IARC.

van Zeller A-M. , & Combes R.D. (1999). Transgenic mouse bioassays for carcinogenicity testing: a step in the right direction? ATLA 27, 839–846.

Combes R. , Balls M. , Curren R. , Fischbach M. , Fusenig N. , Kirkland D. , Lasne C. , Landolph J. , LeBoeuf R. , Marquardt H. , McCormick J. , Müller L. , Rivedal E. , Sabbioni E. , Tanaka N. , Vasseur P. , & Yamasaki H. (1999). Cell transformation assays as predictors of human carcinogenicity. The report and recommendations of ECVAM workshop 39. ATLA 27, 745–767.

Mareel M.M. , Kint J. , & Meyvisch C. (1979). Methods of study of the invasion of malignant C3H-mouse fibroblasts into embryonic chick heart in vitro. Cell Pathology 30, 95–111.

Smolle J. , Helige C. , & Tritthart H.A. (1992). An image analysis and statistical evaluation program for the assessment of tumor cell invasion in vitro. Analytical Cellular Pathology 4, 49–57.

Fusenig N.E. , & Boukamp P. (1998). Multiple stages and genetic alterations in immortalization, malignant transformation, and tumor progression of human skin keratinocytes. Molecular Carcinogen-esis 23, 144–158.

DeVaney T.T. , Tritthart H.A. , Ahammer H. , & Helige C. (1997). In vitro evaluation of cancer cell invasiveness by confocal laser scan techniques. In Animal Alternatives, Welfare and Ethics. (ed. van Zutphen L.F.M. , & Balls M. ), pp. 329–335. Amsterdam, The Netherlands: Elsevier.

Tsuchiya T. , Umeda M. , Nishiyama H. , Yosh-imura I. , Ajimi S. , Asakura M. , Bab H. , Dewa Y. , Ebe Y. , Fushiwaki Y. , Hamada S. , Hamamura T. , Hayashi M. , Iwase Y. , Kajiwara Y. , Kasahara Y. , Kawabata M. , Kitada E. , Kubo K. , Mashiko K. , Miura D. , Mizuhashi F. , Mizuno F. , Nakajima M. , Nakamura Y. , Nobe N. , Oishi H. , Ota E. , Sakai A. , Sato M. , Shimada S. , Sugiyama T. , Takahashi C. , Takeda Y. , Tanaka N. , Toyoizumi C. , Tsutsui T. , Wakauri S. , Yajima S. , & Yajima N. (1999). An interlaboratory validation study of the improved transformation assay employing Balb/c 3T3 cells: results of a collaborative study on the two-stage cell transformation assay by the Non-genotoxic Carcinogen Study Group. ATLA 27, 685–702.

Cohen S.M. , Robinson D. , & MacDonald J. (2001). Alternative models for carcinogenicity testing. Toxicological Sciences 64, 14–19.

Mauthe R.J. , Gibson D.P. , Bunch R.T. , & Custer L. (2001). The Syrian hamster embryo (SHE) cell transformation assay: review of the methods and results. Toxicologic Pathology 29, Suppl., 138–146.

LeBoeuf R.A. , Kerckaert G.A. , Aardema M.J. , Gibson D.P. , Brauninger R. , & Isfort R.J. (1996). The pH 6.7 Syrian hamster embryo cell transformation assay for assessing the carcinogenic potential of chemicals. Mutation Research 356, 85–127.

LeBoeuf R.A. , Kerckaert K.A. , Aardema M.J. , & Isfort R J. (1999). Use of Syrian hamster embryo and Balb/c 3T3 cell transformation for assessing the carcinogenicity potential of chemicals. In IARC Scientific Publications No. 146: The Use of Short-and Medium-term Tests for Carcinogenic Hazard Evualuation (ed. McGregor D.B. , Rice J.M. , & Venitt S. ), pp. 409–425. Lyon, France: IARC.

Combes R.D. (2000). Endocrine disruptors – a critical review of in vitro and in vivo testing strategies for assessing their toxic hazard to humans. ATLA 28, 81–118.

Ashby J. , & Paton D. (1993). The influence of chemical structure on the extent and sites of carcinogenesis for 522 rodent carcinogens and 55 different human carcinogen exposures. Mutation Research 286, 3–74.

Barratt M.D. (2000). Principles of toxicity prediction from chemical structure. In Progress in Reduction, Refinement and Replacement in Animal Experimentation (ed. Balls M. , van Zeller A-M. , & Halder M.E. ), pp. 449–456. Amsterdam, The Netherlands: Elsevier.

Dearden J.C. , Barratt M.D. , Benigni R. , Bristol D.W. , Combes R.D. , Cronin M.T.D. , Judson P.M. , Payne M.P. , Richard A.M. , Tichy M. , Worth A.P. , & Yourick J.J. (1997). The development and validation of expert systems for predicting toxicity. The report and recommendations of an ECVAM/ECB workshop (ECVAM workshop 24). ATLA 25, 223–252.

Klopman G. , & Rosenkranz H.S. (1994). Approaches to SAR in carcinogenesis and mutagenesis. Prediction of carcinogenicity/mutagenicity using MULTICASE. Mutation Research 305, 33–46.

Ridings J.E. , Barratt M.D. , Cary R. , Earnshaw C.G. , Eggington C.E. , Ellis M.K. , Judson P.N. , Langowski J.J. , Marchant C.A. , Payne M.P. , Watson W.P. , & Yih T.D. (1996). Computer prediction of possible toxic action from chemical structure: an update on the DEREK system. Toxicology 106, 267–279.

Long A. , & Combes R.D. (1995). Using DEREK to predict the activity of some carcinogens/mutagens found in foods. Toxicology in Vitro 9, 563–569.

Parry J.M. (1994). Detecting and predicting the activity of rodent carcinogens. Mutagenesis 9, 3–5.

Lewis D.F. , & Langley G.R. (1996). A validation study of the COMPACT and HazardExpert techniques with 40 chemicals. Mutation Research 369, 157–174.

Lewis D.F.V. , Ioannides C. , & Parke D.V. (1996). COMPACT and molecular structure in toxicity assessment: a prospective evaluation of 30 chemicals currently being tested for rodent carcinogenicity by the NCI/NTP. Environmental Health Perspectives 104S, 1011–1016.

Benigni R. (2000). Structure–activity relationships in mutagenesis and carcinogenesis. In Progress in Reduction, Refinement and Replacement in Animal Experimentation (ed. Balls M. , van Zeller A-M. , & Halder M.E. ), pp. 469–478. Amsterdam, The Netherlands: Elsevier.

Parry E.M. , & Parry J.M. (1995). In vitro cytogenetics and aneuploidy. In Environmental Mutagenesis (ed. Phillips D.H. , & Venitt S. ), pp. 121–139. Oxford, UK: S.Bios Scientific Publishers.

Parry E.M. , Henderson L. , & Mackay J.M. (1995). Procedures for the detection of chemically induced aneuploidy: recommendations of a UK Environmental Mutagen Society working group. Mutagenesis 10, 1–14.

Anon. (1997). ECETOC Monograph No. 27: Aneuploidy. 172 pp. Brussels, Belgium: European Centre for Ecotoxicology and Toxicology of Chemicals.

Fan A.M. , & Howd R.A. (2001). Quantitative risk assessment of nongenotoxic carcinogens. In Genetic Toxicology and Cancer Risk Assessment (ed. Choy W.N. ), pp. 299–320. New York, NY, USA: Marcel Dekker.

Blaauboer B.J. , Barratt M.D. , & Houston J.B. (1999). The Integrated Use of Alternative Methods in Toxicological Risk Evaluation. ECVAM integrated testing strategies task force report 1. ATLA 27, 229–237.

Butterworth B.E. , Connolly R.B. , & Morgan K.T. (1995). A strategy for establishing mode of action of chemical carcinogens as a guide for approaches to risk assessments. Cancer Letters 93, 129–146.

Fielden M.R. , & Zacharewski T.R. (2001). Challenges and limitations of gene expression profiling in mechanistic and predictive toxicology. Toxicological Sciences 60, 6–10.

Fry J. , & George E. (2001). In vitro toxicology in the light of new technologies. ATLA 29, 745–748.