https://mmbr.asm.org/content/mmbr/48/1/60.full.pdf

Mutagenesis and inducible responses to deoxyribonucleic acid damage in Escherichia coli.

The SOS chromotest is reviewed through over 100 publications corresponding to the testing of 751 chemicals. 404 (54%) of these chemicals present a genotoxic activity detectable in the SOS chromotest. Their SOS inducing potencies span more than 8 orders of magnitude. For 452 compounds, the results obtained in the SOS chromotest could be compared to those obtained in the Ames test. It was found that 373 (82%) of these compounds give similar responses in both tests (236 positive and 137 negative responses). Thus the discrepancies between both tests concern 79 compounds (18%). A case by case analysis shows that many of these compounds are at the same time very weak SOS inducers and very weak mutagens. Thus we think that, most of the time, the discrepancies between the two tests may be accounted for by differences in the interpretation of the results rather than by the experimental results themselves. However, there are some compounds which are clearly SOS inducers but devoid of mutagenic activity in the Ames test (such as quinoline-1-oxide) and to a larger extent, clearly mutagenic compounds which do not induce the SOS response in the SOS chromotest (such as benzidine, cyclophosphamide, acridines, ethidium bromide). We also analyzed the correlation between SOS induction, mutagenesis and carcinogenesis according to the classification of Lewis. For 65 confirmed carcinogens (class 1), the sensitivity, i.e., the capacity to identify carcinogens, was 62% with the SOS chromotest and 77% with the Ames test. For 44 suspected carcinogens (class 2), the sensitivity was 66% with the SOS chromotest and 68% with the Ames test. Thus, we confirmed previous observations made on 83 compounds that there is a close correlation between the results given by both bacterial tests. The capacity of the Ames test to identify carcinogens is higher than that of the SOS chromotest. However, because the number of false positive compounds was lower in the SOS chromotest, the specificity, i.e., the capacity to discriminate between carcinogens and non-carcinogens of the SOS chromotest, appeared higher than that of the Ames test. Thus, the results of the SOS chromotest and of the Ames test can complement each other. The SOS chromotest is one of the most rapid and simple short-term test for genotoxins and is easily adaptable to various conditions, so that it could be used as an early - perhaps the earliest - test in a battery.

The SOS chromotest: a review

Selection for defective reversion induction, after UV treatment of E. coli K 12, yielded uvm mutants. These mutants exhibited highly reduced or no UV mutability for all loci tested although they were moderately and normally mutable by X-rays and EMS, respectively. Uvm mutations confer only a slight sensitivity to killing by UV and X-rays and no clear sensitivity to the lethal effect of HN2, EMS or MMS. Growth and viability of untreated uvm cells were normal. The properties of uvm mutants are discussed in relation to those of other relevant mutant types and to some actual problems of induced mutagenesis.

Uvm mutants of Escherichia coli K12 deficient in UV mutagenesis. I. Isolation of uvm mutants and their phenotypical characterization in DNA repair and mutagenesis.

The present overview outlines some of the recent research developments leading to a better understanding of the mechanisms which underlie psoralen induced phototoxicity

Recent advances in psoralen phototoxicity mechanism

Nonmelanoma skin cancers, like most malignancies, increase in incidence with increasing age. However, in general they are not due to the aging process but are primarily due to solar radiation. Clinically, squamous cell carcinomas and basal cell epitheliomas are the most common cancers that occur in the Caucasian population in the United States. The role of radiation from the sun was suggested by a number of astute clinical observations reported around 1900 and subsequently has been established by epidemiologic and experimental studies. Action spectrum evaluations indicate that the ultraviolet B (UVB) rays are the most carcinogenic. However, recent studies indicate that the UVA rays can augment the cancer-producing effects of UVB rays. Other physical stimuli, including heat and wind, can also accelerate UVB carcinogenesis. Chemicals such as the polycyclic hydrocarbons, the nitrosoureas, and nitrogen mustard have an additive carcinogenic effect with UVB radiation. Also, some chemicals such as croton oil, the phorbol ester—TPA, and all- trans -retinoic (RA) acid can promote UVB-initiated carcinogenesis. RA can also inhibit UVB-induced cancer formation. The role of the immune status has received a great deal of attention. Both in experimental and clinical situations, nonspecific immune suppression results in increased cancer formation. Also, recent studies indicate that a specific T cell suppressor population can be induced in experimental animals with UVB which will inhibit rejection of tumors produced by UVB radiation. Finally, damage to DNA by UVB radiation is well established. Studies with the genetic disease xeroderma pigmentosum support the concept that such damage, if not repaired, will lead to cancer formation. It also has been suggested that unrepaired damage to deoxyribonucleic (DNA) and other macromolecules is at least in part responsible for the aging process in general.

Photocarcinogenesis, skin cancer, and aging

Comparative mutagenicity of linear and angular furocoumarins in Escherichia coli strains deficient in known repair functions.

The response to four mutagens (UV radiation, methyl methanesulfonate (MMS), cis -platinum dichlorodiamine ( cis -PDD), and 2-aminopurine (AP)) known to cause different types of DNA damage was investigated in the WP2 strain wild-type for DNA repair and in uvrA − , lexA − , polA − , uvrD − and recL − strains. Each strain was also tested after introduction of either the pKM101 or R648 plasmid. The number of revertants produced by a given mutagen in a given bacterial strain depended in a complex way on: (1) the nature of the mutagen and the type of lesion it created in DNA; (2) the presence and the nature of defects in the chromosomally determined DNA-repair system; and (3) the presence and the nature of plasmids with mutator effect. The results confirm that plasmids enhance mutagenesis through an error-prone DNA-repair system, which is expressed at different levels for different plasmids. Or, alternatively, different repair mechanisms for different plasmids may exist.

R plasmid-mediated enhancement of mutagenesis in strains of Escherichia coli deficient in known repair functions

Mutation induction and killing of V79 Chinese hamster cells by 8-methoxypsoralen plus near-ultraviolet light: Relative effects of monoadducts and crosslinks

Enterobacteriaceae plasmids enhancing chemical mutagenesis and their distribution among incompatibility groups

A series of angelicin derivatives were tested for their mutagenic activity with and without near-ultraviolet irradiation (NUV) in Salmonella typhimurium strains. After irradiation with NUV, the tested compounds induced different numbers of revertants in strain TA100, indicating that the mutational events involved are base substitutions. In the dark, 3 chemicals behaved as frame-shift mutagens causing reversion in strain TA98.

S. Venturini

Papers

Comparative mutagenicity of linear and angular furocoumarins in Escherichia coli strains deficient in known repair functions.

R plasmid-mediated enhancement of mutagenesis in strains of Escherichia coli deficient in known repair functions

Mutation induction and killing of V79 Chinese hamster cells by 8-methoxypsoralen plus near-ultraviolet light: Relative effects of monoadducts and crosslinks

Enterobacteriaceae plasmids enhancing chemical mutagenesis and their distribution among incompatibility groups

Mutagenicity in Salmonella typhimurium of some angelicin derivatives proposed as new monofunctional agents for the photochemotherapy of psoriasis.