A CHO MUTANT, UV40, THAT IS SENSITIVE TO DIVERSE MUTAGENS AND REPRESENTS A NEW COMPLEMENTATION GROUP OF MITOMYCIN-C SENSITIVITY

A new mitomycin C (MMC)-sensitive rodent line, UV40, has been identifi ed in the collection of ultraviolet light-(UV-) sensitive mutants of C hinese hamster ovary (CHO) cells isolated at the previous Facility for Automated Experiments in Cell Biology (FAECB). It was isolated from a n UV mutant hunt using mutagenesis of AA8 cells with the DNA intercala ting frameshift mutagen ICR170. It is complemented by CHO-UV-1, irs1, irs3, irs1SF, MC5, V-C8 and V-H4 with respect to its MMC sensitivity b ased on cell survival. Despite having approx, 4 x normal UV sensitivit y and increased sensitivity to UV inhibition of DNA replication, it ha s near-normal incision kinetics of UV irradiated DNA, and normal (6-4) photoproducts removal. It also is not hypermutable by UV, and shows n ear normal levels of UV inhibition of RNA synthesis. UV40 also has app rox, 11X, 10x, 5x and 2x AA8 sensitivity to MMC, ethyl methanesulfonat e (EMS), methyl methanesulfonate (MMS), and X-rays, respectively. Thus , its defect apparently does not involve nucleotide excision repair bu t rather another process, possibly in replicating past lesions. The sp ontaneous chromosomal aberration frequency is elevated to 20% in UV40, and the baseline frequency of sister chromatid exchange is also simil ar to 4-fold increased. The phenotype of UV40 appears to differ from a ll other rodent mutants that have so far been described.