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Mutagenesis, Vol. 14, No. 1, 141-151, January 1999
© 1999 UK Environmental Mutagen Society/Oxford University Press


Review

Transgenic mouse mutation assay systems can play an important role in regulatory mutagenicity testing in vivo for the detection of site-of-contact mutagens

S.W. Dean1,7, T.M. Brooks1, B. Burlinson2, J. Mirsalis3, B. Myhr4, L. Recio5 and V. Thybaud6

1 Covance Laboratories Ltd, Otley Road, Harrogate HG3 1PY, UK, 2 Glaxo Wellcome, Park Road, Ware SG12 0DJ, UK, 3 SRI International, Toxicology Laboratory, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493, USA, 4 Covance Laboratories Inc., 9200 Leesburg Pike, Vienna, VA 22182, USA, 5 CIIT, Research Triangle Park, NC 27709, USA and 6 Rhone Poulenc Rorer, Alfortville, 14 94403 Vitry-sur-Seine Cedex, France

Transgenic mouse mutation assays, such as MutaTMMouse (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 MutaTMMouse 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.

7 To whom correspondence should be addressed. Tel: +44 1 423 500011; Fax: +44 1 423 569595; Email: stephen.dean{at}covance.com


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