Role of Cellular Systems in Modifying the Response to Chemical Mutagens
Neocarzinostatin (NCS) produces apurinic/apyrimidinic (AP) sites in DNA which are repaired by the AP excision repair system. Survival after NCS treatment is not determined exclusively by this repair system, presumably because of the production of other, lethal, lesions. MNNG also produces multiple lesions which may be handled by cells in different ways. In E. coli, MNNG treatment results in rapid induction of a system which removes O6-methylguanine. Inhibition of this induction with chloramphenicol results in a large increase in mutation frequency. Induction of an enzyme which removes O6-methylguanine probably accounts for the enrichment of mutations near DNA growing points. MNNG also induces multiple closely linked mutations. The production of multiple mutations but not of single-site mutations is blocked in rec A and uvr E strains. The exact nucleotide site at which DNA synthesis is blocked in vitro by reaction with mutagens can be observed in a øX174 system in which the nucleotide sequence is known. DNA polymerase I catalyzed synthesis is blocked one nucleotide before the reacted base on the template strand. In contrast, with some damaged templates, AMV reverse transcriptase can insert a base at the level of the reacted nucleotide on the template.
KeywordsXeroderma Pigmentosum Repair Synthesis Single Site Mutation Dose Reduction Factor MNNG Treatment
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- 13.Hutchinson, C., S. Phillips, M. Edgell, S. Gillam, P. Jahnke, and M. Smith, Mutagenesis at a specific position in a DNA sequence, J. Biol. Chem., 253 (1978) 6551–6560.Google Scholar
- 17.Maaloe, O., and N. Kjeldgaard, Control of Macromolecular Synthesis, W. A. Benjamin, New York, 1966.Google Scholar
- 20.Prakash, L., The relation between repair of DNA and radiation and chemical mutagenesis in Saccharomyces cerevisiae, Mutat. Res., 41 (1976) 244–248.Google Scholar
- 26.Scudiero, D., E. Henderson, A. Norin, and B. Strauss, The measurement of chemically-induced DNA repair synthesis in human cells by BND-cellulose chromatography, Mutat. Res., 29 (1975).Google Scholar
- 31.Tatsumi, K., Unpublished data.Google Scholar
- 34.Weinstein, I. G., and D. Grunberger, Structural and functional changes in nucleic acids modified by chemical carcinogens, In: Chemical Carcinogenesis, Part A, P. Ts’o and J. DiPaolo, Eds., Marcel Dekker, New York, 1974, pp. 217–235.Google Scholar