Analysis of sister chromatid exchanges directly in G2-phase lymphocyte prematurely condensed chromosomes: A new cytogenetic approach for risk assessment of chemical in vitro exposures to cytotoxic levels

Sister chromatid exchange (SCE) analysis in human peripheral blood lymphocytes is often applied as a cytogenetic assay for biomonitoring and genotoxicity testing of potentially mutagenic and carcinogenic chemicals. Sister chromatid exchanges (SCEs) represent the interchange of DNA replication products at apparently homologous sites on the two chromatids of a single chromosome, and are indicative of DNA damage corrected by recombinational repair. Such a strand recombination (crossover) is believed to be the basis for the formation of SCEs. It has been found that S-phase dependent agents are very good inducers of SCEs, whereas ionizing radiation is a poor inducer (1). The evidence of SCE formation came from early studies (2) that demonstrated their occurrence during replication of chromosomes and paved the way to detect them easily. A breakthrough in the visualization of SCEs came in 1972-1974. It was then shown that, when a thymidine analogue such as 5-bromodeoxyuridine (BrdU) is incorporated into the DNA for two cell cycles, the sister chromatids, which are different, namely bifilarily and unifilirily incorporated BrdU (BB-TB), can be distinguished using Giemsa staining, fluorescence dyes, or their combination. The fluorescence plus Giemsa (FPG) technique (3) became popular because of the ease with which the technique can be performed and also because the slides can be stored for a long time. At present, however, there are two main practical problems with respect to the use of SCE analysis for genotoxicity testing of possible human carcinogens.