ON THE ROLE OF DNA DOUBLE-STRAND BREAKS IN TOXICITY AND CARCINOGENESIS

DNA double-strand breaks are associated with various endogenous proces ses, such as transcription, recombination, replication, and with the p rocess of active cell death, which aims to eliminate cells. In additio n, DNA double-strand breaks can be induced by irradiation, exposure to chemicals, increased formation of reactive oxygen species, and, indir ectly, during repair of other types of DNA damage or as a consequence of extranuclear lesions. In addition to the neutral filter elution of DNA, the recently introduced pulsed-field gel electrophoresis is capab le of determining DNA double-strand breaks with higher accuracy and se nsitivity and is expected to increase our knowledge on the frequency a nd the role of DNA breakage. Parallel determination of parameters for cytotoxicity is necessary to elucidate the causal primary lesion. Alth ough the repair of DNA double-strand breaks is a complex task, cells a re capable of repairing - with or without errors and up to a certain e xtent - and surviving this DNA lesion. Gene translocations, rearrangem ents, amplifications, and deletions arising during repair and misrepai r of double-strand breaks may contribute to cell transformation and tu mor development.