CYTOGENETIC CHARACTERIZATION OF THE TRANSGENIC BIG BLUE(R) RAT2 AND BIG BLUE(R) MOUSE EMBRYONIC FIBROBLAST CELL-LINES

The transgenic Big Blue(R) Rat2 and Big Blue(R) mouse embryonic fibrob last cell lines have been used to complement the transgenic Big Blue(R ) rat and mouse in vivo mutagenesis assays, However, limited informati on is available regarding the karyology of these cell lines. Therefore , we have characterized the ploidy, mitotic index, spontaneous frequen cies of chromosome and chromatid aberrations and rate of micronucleus (MN) formation in both cell lines. We have also characterized the freq uency of sister chromatid exchange (SCE) in transgenic Big Blue(R) mou se cells. Big Blue(R) Rat2 cells are hyperploid and have extremely hig h baseline frequencies of cytogenetic damage. In addition, Big Blue(R) Rat2 cells are BrdU-resistant, therefore, SCE frequencies cannot be a ssessed in these cells, We conclude that Big Blue(R) Rat2 cells are no t useful for routine cytogenetic toxicology studies. The transgenic Bi g Blue(R) mouse cell line is polyploid and consistently yields a low m itotic index (similar to 1%) in untreated cells, These mouse cells als o exhibited moderately high baseline frequencies of chromosome and chr omatid aberrations, however, baseline frequencies of SCE and of MN wer e not elevated. Transgenic Big Blue(R) mouse embryonic fibroblasts wer e further studied for MN induction following treatment with N-ethyl-N- nitrosourea (ENU) for 0.5 h at concentrations of 0.425, 0.85 and 1.7 m M, Concentration-dependent increases in MN were observed in these cell s, Thus, while an ENU-induced cytogenetic response using transgenic Bi g Blue(R) mouse cells demonstrates that this cellular model could be u sed to cytogenetically complement the mutagenesis assays, the low mito tic index and the high spontaneous frequency of chromosome damage conf ounds its use for routine genetic toxicology studies.