Chemically induced mutation of L5178Y mouse leukemia cells from asparagine-dependence to asparagine-independence

L₅₁₇8Y mouse lymphoblastic leukemia cells are auxotrophic for l-asparagine (ASN) and have been widely used as a model system for studies on l-asparagine independence, were treated with known chemical mutagens to investigate the molecular basis of this mutation. Mutagens which primarily induce base pair substitutions—ethyl methanesullfonate (EMS) and N-methyl-N′-nitro-N-nitrosoguanidine (MNNG)—as well as those which induce frame-shift mutations (the acridine half-mustards ICR-₃₇₂ and ICR-191) each increased the frequency of ASN⁺ cells in treated cultures to at least ten times the usual background frequency of 1 to 2 ASN⁺ cells per 10⁶ cells. The effectiveness of both classes of mutagens indicates that the change to asparagine prototrophy might occur by a mechanism other than, or in addition to, reversion of a specific base pair, point mutation. The mutability of this easily assayed nutritional genetic marker in a cell line that can be grown either in vitro or in vivo may provide a useful system for assay of other agents of unknown mutagenic potential.