Improvements in the reliability of in vitro genotoxicity testing.

Abstract:

INTRODUCTION:In vitro genotoxicity assays have a high sensitivity to detect rodent carcinogens, but mammalian cell tests have a propensity for misleading positive results (poor specificity). Recent data show a greater risk of misleading positive results in p53-deficient rodent cell lines than in p53-competent human cells. Measures of cytotoxicity, source and stability of cells used are also important. AREAS COVERED:In this review, potential reduction in the top concentration for testing (10 mM) is discussed. Indirect effects on non-DNA targets, which may not be relevant for humans or may exhibit a threshold, have been identified. EXPERT OPINION:The reliability of in vitro genotoxicity tests could be improved by selecting p53-proficient, human cells. The provenance and stability of the cells used should be demonstrated. Measures of cytotoxicity based on cell proliferation should be used. Lowering the top concentration for testing from 10 mM to 4 mM or 2000 μg/ml, whichever is the lower, as proposed by some experts, would seem to be justified. Artefacts that may be caused by reaction of test substance with culture medium should be avoided. Better understanding and investigation of the potential for threshold and irrelevant modes of action are encouraged.

authors

Kirkland D

doi

10.1517/17425255.2011.627855

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

1513-20

issue

12

eissn

1742-5255

issn

1744-7607

journal_volume

7

pub_type

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