The Use of Short- and Medium-term Tests for Carcinogens and Data on Genetic Effects in Carcinogenic Hazard Evaluations

by D. B. McGregor; J. M. Rice; S. Venitt

• ISBN13: 9789283221463
• ISBN10: 928322146X
• Edition: 1st
• Format: Paperback
• Copyright: 1999-06-03
• Publisher: STYLUS PUBLISHING LLC

Summary

Lifetime assays for carcinogenicity in experimental animals, together with data on genetic and related effects on a variety of organisms, have long been the foundation for predictions of carcinogenic hazard to human beings. Recent scientific advances have provided new assays and novel test systems that are beginning to supplement, and in the future may even replace, the well-established tests that have been widely used for the last four decades. This publication reviews the evidence that justifies the use of lesions that precede histologically defined malignancy as endpoints to predict carcinogenicity. It evaluates the utility of non-mammalian species and of genetically engineered rodents as subjects for carcinogenicity tests and mutations in cancer-related genes in human and experimental animal tumours as 'footprints' of environmental carcinogens. It evaluates the use of established and novel assays for genetic toxicity in the prediction of carcinogenicity. Finally it formulates recommendations on the use of such data in the process of evaluation of carcinogenic hazards by the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans.

Table of Contents

Consensus report	1	(18)
Mutations and altered expression of human cancer genes: What they tell us about causes	19	(24)
T.R. Devereux
J.I. Risinger
J.C. Barrett
Analysis of somatic mutations of the p53 gene in human cancers: A tool to generate hypotheses about the natural history of cancer	43	(12)
T. Hernandez-Boussard
R. Montensano
P. Hainaut
Mutations in ras genes in experimental tumours of rodents	55	(32)
R.C. Sills
G.A. Boorman
J.E. Neal
H.L. Hong
T.R. Devereux
Mutation patterns in non-ras oncogenes and tumour suppressor genes in experimentally induced tumours	87	(36)
A.O. Perantoni
J.M. Rice
Genetically altered mouse models for identifying carcinogens	123	(28)
R.W. Tennant
S. Stasiewicz
J. Mennear
J.E. French
J.W. Spalding
Use of non-mammalian species in bioassays for carcinogenicity	151	(34)
T.E. Bunton
Chemically induced preneoplastic lesions in rodents as indicators of carcinogenic activity	185	(18)
G.M. Williams
Short-and medium-term carcinogenicity tests: Simple initiation-promotion assay systems	203	(48)
H. Tsuda
C.B. Park
M.A. Moore
Medium-term bioassays in rats for rapid detection of the carcinogenic potential of chemicals	251	(22)
T. Shirai
M. Hirose
N. Ito
Active cell death (apoptosis) and cellular proliferation as indicators of exposure to carcinogens	273	(14)
R. Schulte-Hermann
W. Bursch
B. Marian
B. Grasl-Kraupp
DNA adducts in mammalian cells as indicators of exposure to carcinogens	287	(22)
D.E.G. Shuker
DNA damage and repair in mammalian cells in vitro and in vivo as indicators of exposure to carcinogens	309	(46)
D. McGregor
D. Anderson
Mutation in mammalian cells in vitro and in vivo as indicators of exposure to carcinogens	355	(12)
A.A. van Zeeland
H. Vrieling
Induction of mutations in transgenic animal models: BigBlue™ and Muta™Mouse	367	(28)
P. Schmezer
C. Eckert
Chromosomal changes	395	(14)
R.J. Preston
Use of Syrian hamster embryo and BALB/c 3T3 cell transformation for assessing the carcinogenic potential of chemicals	409	(18)
R.A. LeBoeuf
K.A. Kerckaert
M.J. Aardema
R.J. Isfort
The results of assays in Drosophila as indicators of exposure to carcinogens	427	(44)
E.W. Vogel
U. Graf
H.-J. Frei
M.M.J. Nivard
Use of tests in yeasts and fungi in the detection and evaluation of carcinogens	471	(16)
J.M. Parry
Identification of carcinogenic substances by means of short-term tests in bacteria	487	(12)
P. Quillardet
D. McGregor
Short-term tests for defining mutagenic carcinogens	499
M.D. Waters
H.F. Stack
M.A. Jackson