Bacterial mutagenesis: Review of new insights

Abstract

I NTR OD UCT 1 0 NPotentially mutagenic lesions occur repeatedly in the DNA of living organisms. Only the presence of exceptionally active DNA repair systems prevents rapid loss of genetic fidelity. Recent publications cited in this short review demonstrate that bacteria continue to provide valuable insights into DNA-repair mechanisms and mutagenesis. Bacteria also serve as a principal short-term screen for detection and analysis of environmental agents responsible for increasing the endogenous load of mutational lesions in mammalian DNA. These aspects of research utilizing bacteria are important, for they clearly have applicability to the cancer problem (see [ l ] for an excellent review). Additionally, mutagens may contribute substantially in other ways to the demise of human health, for example by induction of "benign," "preneoplastic" foci that may comprise a significant component of aging [ 2 ] . In this article I review a few highlights of current research that have attracted my attention. Because my description is highly abridged, the reader is referred to the literature cited for details and for references to the longer history that underlies each development mentioned. Kimball Table I indicates that fidelity in bacterial DNA replication is preserved through a multistep sequence which includes, successively: 1) Watson-Crick base pairing subject to a high error frequency, particularly "transition" (purine-for-purine and pyrimidine-forpyrimidine) base substitution mutations; 2) a base-selection mechanism by the DNA polymerase; 3) a 3' + 5' editing or proofreading function that removes mismatched bases at the 3' terminus of the newly replicated strand at the time of synthesis.These first three steps ensure a high degree of fidelity in DNA replication in vitro by Polymerase I of E coli, with a measured apparent error frequency for dCTP incorporation

Genotoxic classification of anticancer drugs

“…Excision repair is the major error-free DNA repair system of most living organisms including bacteria and man [22,23]. Although direct extrapolation from bacteria to man is impossible, a drug whose premutational lesions are readily removed by bacterial excision repair should, theoretically at least, constitute less of a threat to man than a drug whose mutagenic activity can take place in repair proficient bacterial test strains.…”

The effects of excision repair and the plasmid pKM101 on the induction of his+revertants by chemical agents inSalmonella typhimurium

“…This classification may provide an initial step in risk estimation. Since excision repair is the major error-free method of removing all types of lesions which cause molecular distortions in DNA [21] both in bacteria and in man [22], class I and I1 mutagens may pose a more formidable threat to either organism than a class I11 mutagen. This would mean that while one must always reduce exposure to known mutagens to a minimum, including class I11 mutagens, there would be much higher probability of demonstrating environmentally induced carcinogenesis-for example, in populations having prolonged exposures to low doses of class I or I1 mutagens than to class 111 substances.…”

History of Environmental and Molecular Mutagenesis

“…Those who turned out to be the next three editors had been appointed to editorial positions, and Philip E. Hartman had taken on the role of reviews editor. Phil Hartman was the author of the first review article in the journal [Hartman, 1980] and officially became the reviews editor in 1983, although he had already been soliciting reviews for the journal for some time. He approached this role with the same combination of generosity, dedication, and brilliance that characterized his life as a whole [Cebula, 2003].…”