Mouse lymphoma thymidine kinase gene mutation assay: follow-up International Workshop on Genotoxicity Test Procedures, New Orleans, Louisiana, April 2000.
The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on Genotoxicity Test Procedures held a second harmonization meeting just prior to the U.S. Environmental Mutagen Society Meeting in New Orleans, LA, in April 2000. The discussion focused on several important aspects of the MLA, including: 1) cytotoxicity measures and their determination, 2) use of a 24-hr treatment, 3) the ability of the assay to detect aneugens, and 4) concentration selection. Prior to the meeting the group developed Microsoft Excel Workbooks for data entry. Ten laboratories entered their data into the workbooks (primarily as coded chemicals). The Excel Workbooks were used to facilitate data analysis by generating an extensive set of graphs that were evaluated by the meeting participants. Based on the Workgroup's previous agreement that a single cytotoxicity measure should be established for both the microwell and soft agar versions of the assay, the Workgroup analyzed the submitted data and unanimously agreed that the relative total growth (RTG) should be used as the cytotoxicity measure for concentration selection and data evaluation. The Workgroup also agreed that the various cytotoxicity measures should be calculated using the same methods regardless of whether the soft agar or microwell version of the assay was used. In the absence of sufficient data to make a definitive determination, the Workgroup continued to endorse the International Committee on Harmonization recommendation for the use of 24-hr treatment and made some specific 24-hr treatment protocol recommendations. The Workgroup recognized the ability of the MLA to detect at least some aneugens and also developed general guidance and requirements for appropriate concentration selection.
Moore
Martha M
MM
National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, USA.
Honma
Masamitsu
M
Clements
Julie
J
Harrington-Brock
Karen
K
Awogi
Takumi
T
Bolcsfoldi
George
G
Cifone
Maria
M
Collard
Deborah
D
Fellows
Michael
M
Flanders
Kathryn
K
Gollapudi
Bhaskar
B
Jenkinson
Peter
P
Kirby
Paul
P
Kirchner
Stephan
S
Kraycer
Joann
J
McEnaney
Stephen
S
Muster
Wolfgang
W
Myhr
Brian
B
O'Donovan
Michael
M
Oliver
Jo
J
Ouldelhkim
Marie-Claude
MC
Pant
Kamala
K
Preston
Robert
R
Riach
Colin
C
San
Richard
R
Shimada
Hiroyasu
H
Stankowski
Leon F
LF
D000818:Animals; D004493:Education; D017408:Guidelines as Topic; D008223:Lymphoma / Q000201:enzymology*; D051379:Mice; D009152:Mutagenicity Tests / Q000379:methods*; D009154:Mutation; D013937:Thymidine Kinase / Q000235:genetics*; D013997:Time Factors
D013937:Thymidine Kinase