The object of this research is to determine the role of single-gene mutation versus extra-mutational events such as mitotic recombination, non-disjunction, or segregation, in the expression of DNA damage or pre-existing recessive mutations in cultured mammalian cells. We propose to specific-locus mutagenesis by various classes of physical or chemical mutagens at multiple gene loci, using a Chinese hamster ovary cell subline that is functionally heterozygous for the genes for adenine phosphoyribosyl transferase and thymidine kinase. We propose to determine the effects of known tumor promoters and agents that induce non-disjunction or mitotic recombination, on the expression of recessive mutations in cultured mammalian cells, and whether these agents can act as mutagenesis promoters or co-mutagens. Finally, we propose to examine the effects of exogenous deoxyribonucleoside concentrations or imbalances in deoxyrinbonucleotide pools on spontaneous and induced mutation frequencies.