Abstract: BACKGROUND ＆ AIM： To investigate the mutation frequency and molecular mutation of spontaneous mutations on the tk gene of mouse lymphoma cells. MATERTAL AND METHODS：Performing four times parallel test. Mutation frequency of tk locus were analyzed by the mouse lymphoma assay(microitier procedure), and Loss of heterozygosity(LOH) analysis withallic special PCR. Subsequently, we determined the DNA sequence of negative LOH's clones. RESULTS：Loss of heterozygosity analysis of the tk locus revealed that the most spontaneous mutants lost the functional tk allele (average LOH 79.8％). LOH of spontaneous mutations showed there were no significant difference between large clone(LC) and small clone(SC).Spontaneous mutations were substitutions, and most of them were transversions. CONCLUSION： Functional tk allic gene lose was major mutational event in spontaneous mutations and point mutations were substitutions.

Key words: spontaneous mutations, tk locus, loss of heterozygosity, molecular mutation