THE ROLE OF MITOTIC RECOMBINATION IN CARCINOGENESIS

Genetic recombination systems are present in all living cells and viru ses and generally contribute to their hosts' flexibility with respect to changing environmental conditions. Recombination systems not only h elp highly developed organisms to protect themselves from microbial at tack via an elaborate immune system, but conversely, recombination sys tems also enable microorganisms to escape from such an immune system. Recombination enzymes act with a high specificity on DNA sequences tha t either exhibit extended stretches of homology or contain characteris tic signal sequences. However, recombination enzymes may rarely act on incorrect alternative target sequences, which may result in the forma tion of chromosomal deletions, inversions, translocations, or amplific ations of defined DNA regions. This review describes the characteristi cs of several recombination systems and focuses on the implication of aberrant recombination in carcinogenesis. The consequences of mitotic recombination on the inappropriate activation of protooncogenes and on the loss of tumor suppressor genes is discussed. Cases are reported w here mitotic recombination clearly has been associated with carcinogen esis in rodents as well as humans. Several test systems able to detect recombinagenic activities of chemical compounds are described.