PMID- 10737955
OWN - NLM
STAT- MEDLINE
DCOM- 20000427
LR  - 20141120
IS  - 0893-6692 (Print)
IS  - 0893-6692 (Linking)
VI  - 35
IP  - 3
DP  - 2000
TI  - Appropriate levels of cytotoxicity for genotoxicity tests using mammalian cells 
      in vitro.
PG  - 202-5
AB  - Among standard battery genotoxicity assays, the in vitro chromosome aberration 
      test and the mouse lymphoma tk assay (MLA) yield about fourfold higher incidences 
      of positive test results than the bacterial reverse mutation test or in vivo bone 
      marrow tests. This is a result of experience with submissions of 335 new 
      pharmaceuticals to the German Federal Institute for Drugs and Medical Devices. 
      While all of the standard systems have their value in detecting relevant 
      genotoxins, there is no supportive evidence for DNA reactivity for a considerable 
      number of in vitro clastogens and MLA positives. In particular the clastogenic 
      response of such compounds is often associated with high cytotoxicity. This may 
      invoke the need to change the approach to test for clastogenicity in vitro. A 
      combination of measures such as (1) a change in the upper limits of cytotoxicity 
      that are currently given in International Conference on Harmonisation (ICH) and 
      Organization for Economic Co-Operation & Economic Development (OECD) guidelines, 
      (2) the creation of a common ground of understanding for interpretation of in 
      vitro (positive) test results, and (3) lowering the upper limits of test compound 
      concentration irrespective of cytotoxicity may prove useful to ensure a 
      sufficient reliability of genotoxicity testing with mammalian cells in vitro.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Muller, L
AU  - Muller L
AD  - Federal Institute for Drugs and Medical Devices, Berlin, Germany. 
      L.mueller@bfarm.de
FAU - Sofuni, T
AU  - Sofuni T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Environ Mol Mutagen
JT  - Environmental and molecular mutagenesis
JID - 8800109
SB  - IM
MH  - Animals
MH  - *Cell Survival
MH  - Guidelines as Topic
MH  - In Vitro Techniques
MH  - Lymphoma/genetics/*pathology
MH  - Mammals
MH  - Mice
MH  - *Mutagenicity Tests
MH  - Tumor Cells, Cultured
EDAT- 2000/03/29 09:00
MHDA- 2000/04/29 09:00
CRDT- 2000/03/29 09:00
PHST- 2000/03/29 09:00 [pubmed]
PHST- 2000/04/29 09:00 [medline]
PHST- 2000/03/29 09:00 [entrez]
AID - 10.1002/(SICI)1098-2280(2000)35:3<202::AID-EM7>3.0.CO;2-Q [pii]
PST - ppublish
SO  - Environ Mol Mutagen. 2000;35(3):202-5.