Transgenic mouse mutation assay systems can play an important role in regulatory mutagenicity testing in vivo for the detection of site-of-contact mutagens.
Transgenic mouse mutation assays, such as MutaMouse (lacZ, CD2F1) and Big Blue (lacI, B6C3F1), afford the opportunity to evaluate the mutagenic potential of chemicals in any target organ in vivo. This paper discusses published data collected from the analysis of the skin, stomach and lung DNA after topical, oral and inhalation exposure, respectively. These data indicate that both MutaMouse and Big Blue should play an important part in the evaluation of genotoxicity in vivo, particularly where the endpoint or target tissue available in the more conventional tests is inappropriate. It is concluded that there is a distinct role for this type of assay in genetic toxicology testing. For substances applied to the skin or dosed orally or by inhalation and which are unlikely to reach either the bone marrow or the liver, then data derived from these assays may be more relevant to an assessment of possible risk to man than the currently used unscheduled DNA synthesis in liver and cytogenetics assays in bone marrow or peripheral blood.
Dean
S W
SW
Covance Laboratories Ltd, Harrogate, UK. stephen.dean@covance.com
Brooks
T M
TM
Burlinson
B
B
Mirsalis
J
J
Myhr
B
B
Recio
L
L
Thybaud
V
V
D000818:Animals; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D009152:Mutagenicity Tests / Q000379:methods* / Q000639:trends; D009153:Mutagens / Q000032:analysis*; D009154:Mutation / Q000235:genetics*
D009153:Mutagens