Strand breaks arising from the repair of the 5-bromodeoxyuridine-substituted template and methyl methanesulphonate-induced lesions can explain the formation of sister chromatid exchanges.
5-Bromodeoxyuridine (BrdU)-induced sister chromatid exchanges (SCEs) are mainly determined during replication on a BrdU-substituted template. The BrdU, once incorporated, is rapidly excised as uracil (U), and the gap is repaired with the incorporation of BrdU from the medium, which leads to further repair. During the second S period in BrdU medium, this process continues as the strand acts as template. Experiments suggest that 3-aminobenzamide (3AB) delays the ligation of the gaps formed after U excision, resulting in enhanced SCE levels during the second cycle of BrdU incorporation. When normal templates of G1 cells are treated before BrdU introduction with methyl methanesulphonate (MMS), 3AB in the first cycle doubles the MMS-induced SCEs but has no effect on them during the second cycle. When the BrdU-substituted template is treated with MMS in G1 of the second cycle, 3AB again doubles the SCEs due to MMS and also enhances the SCEs resulting from delays in ligation of the gaps following U excision in the BrdU-substituted template. The repair processes of MMS lesions that are sensitive to 3AB and lead to SCEs take place rapidly, while the repair process of late repairing lesions that lead to SCEs appear to be insensitive to 3AB. A model for SCE induction is proposed involving a single-strand break or gap as the initial requirement for SCE initiation at the replicating fork. Subsequent events represent natural stages in the repair process of a lesion, ensuring replication without loss of genetic information.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000032:analysis / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000302:isolation & purification; D004260:DNA Repair; D003857:Deoxyuridine / Q000032:analysis; D005260:Female; D007700:Kinetics; D008741:Methyl Methanesulfonate / Q000494:pharmacology*; D010053:Ovary; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013698:Templates, Genetic
D001549:Benzamides; C025160:3-aminobenzamide; D004247:DNA; D008741:Methyl Methanesulfonate; D001973:Bromodeoxyuridine; D003857:Deoxyuridine