ABSTRACT
I. INTRODUCTION The many genotoxicity tests that have been developed over the past years offer a variety of systems (prokaryotic, eukaryotic, in vitro, and in vivo) and endpoints (gene mutation, chromosome aberration, DNA damage). Those that use mammalian cells have the advantage of more closely approximating the human system and gene mutations that occur in mammalian cells and appear to be relevant for human genetic disorders, including cancers. The mouse lymphoma assay (MLA) quantifies genetic alterations that affect expression of the thymidine kinase (TK) gene (tk) in mouse L5178Y tk+/– lymphoma cells. Because the MLA can detect a wide range of genetic alterations (point mutations, larger scale chromosomal changes, recombination, mitotic nondisjunction, and others) (Fig. 1), it has been regarded as the most sensitive in vitro mammalian cell gene mutation assay (1-8). Most of the alterations detected by the test are found in human tumor cells and are presumably relevant for carcinogenesis (9). Compared with other genotoxicity tests, the MLA is capable of detecting mutagens and clastogens, which can be detected by the bacterial reverse mutation assay (Ames test) and the chro-
. 1.
