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

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

Schultz, B. D., A. K. Singh, D. C. Devor, and R. J. Bridges. Pharmacology of CFTR Chloride Channel Activity. Physiol. Rev. 79, Suppl.: S109–S144, 1999. — The pharmacology of cystic fibrosis transme...

Pharmacology of CFTR Chloride Channel Activity

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

In vitro genotoxicity testing needs to include tests in both bacterial and mammalian cells, and be able to detect gene mutations, chromosomal damage and aneuploidy. This may be achieved by a combination of the Ames test (detects gene mutations) and the in vitro micronucleus test (MNvit), since the latter detects both chromosomal aberrations and aneuploidy. In this paper we therefore present an analysis of an existing database of rodent carcinogens and a new database of in vivo genotoxins in terms of the in vitro genotoxicity tests needed to detect their in vivo activity. Published in vitro data from at least one test system (most were from the Ames test) were available for 557 carcinogens and 405 in vivo genotoxins. Because there are fewer publications on the MNvit than for other mammalian cell tests, and because the concordance between the MNvit and the in vitro chromosomal aberration (CAvit) test is so high for clastogenic activity, positive results in the CAvit test were taken as indicative of a positive result in the MNvit where there were no, or only inadequate data for the latter. Also, because Hprt and Tk loci both detect gene-mutation activity, a positive Hprt test was taken as indicative of a mouse-lymphoma Tk assay (MLA)-positive, where there were no data for the latter. Almost all of the 962 rodent carcinogens and in vivo genotoxins were detected by an in vitro battery comprising Ames+MNvit. An additional 11 carcinogens and six in vivo genotoxins would apparently be detected by the MLA, but many of these had not been tested in the MNvit or CAvit tests. Only four chemicals emerge as potentially being more readily detected in MLA than in Ames+MNvit--benzyl acetate, toluene, morphine and thiabendazole--and none of these are convincing cases to argue for the inclusion of the MLA in addition to Ames+MNvit. Thus, there is no convincing evidence that any genotoxic rodent carcinogens or in vivo genotoxins would remain undetected in an in vitro test battery consisting of Ames+MNvit.

A core in vitro genotoxicity battery comprising the Ames test plus the in vitro micronucleus test is sufficient to detect rodent carcinogens and in vivo genotoxins.

Publisher Summary This chapter describes the photochemistry and photobiology of furocoumarins and the applications of furocoumarins in biology and medicine. Furocoumarins and their congeners are found in many plants. The photoreactivity of psoralens regarding the cycloaddition to DNA is determined by three main factors: kinetic, steric, and electronic. RNA can also be photochemically modified with psoralens and near-UV radiation. When psoralens are intercalated in DNA, the singlet reaction can be a predominant path, because the singlet excited psoralen intercalated need not diffuse too far to encounter its substrate. The probability of the photocycloaddition of psoralen to thymine in solution is enhanced if the excited singlet state of the psoralen encounters thymine and forms an exciplex. In mammalian cells, PUVA-induced mutagenesis is linear with dose, following one-hit kinetics. PUVA treatment is a well-established clastogen. Caffeine enhances the yield of chromosome aberrations when added after PUVA treatment. PUVA treatment inactivates transforming DNA in Bacillus subtilis. DNA cross-links contribute to this effect by preventing entry of DNA into the bacterial cells.

The Photochemistry and Photobiology of Furocoumarins (Psoralens)

pKM101, a plasmid R factor of the N compatibility group increases methylmethane sulfonate mutagenesis and diminishes UV-killing in recA+lex+ and recA+lex− strains, but not in recA−lex+ strains. The induction of a “reclex” dependent colicin is not present in lex− strains carrying the pKM101 factor. These facts indicate that pKM101 acts through an error-prone DNA repair system, which is recA+ dependent, but not lex+ dependent.

Expression of the plasmid pKM101-determined DNA repair system in recA − and lex − strains of Escherichia coli

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

SUMMARY

The monofunctional furocoumarins, the 6-methylangelicins, were tested for their antiproliferative activity with various animal models and for genotoxicity in micro-organisms and in mammalian cells. The most active compound was 6,4,4′-trimethylangelicin, which showed a high antiproliferative effect and reduced genotoxicity in comparison with 8-methoxypsoralen (8-MOP). Some of these compounds were also tested clinically by topical application on 17 patients with psoriasis. They appeared to be more active than 8-MOP in clearing psoriasis without inducing skin phototoxicity. The methylangelicins also caused skin pigmentation.

6‐Methylangelicins: new monofunctional photochemotherapeutic agents for psoriasis

N and I group plasmids, which increase methylmethane sulfonate (MMS) mutagenesis in lexA+ strains of E. coli WP2 may be divided into two classes: those restoring part of the mutability of lexA- strains (class I) and those leaving lexA- strains non-mutable (class II). Almost complete restoration of MMS mutability is obtained by class I plasmids in a partially suppressed lexA rnm strain, while class II plasmids cause far fewer MMS revertants in this strain than in lexA+. A pair of class I and II plasmids in lexA- shows a synergistic effect on mutability. These two classes do not coincide with plasmid division into incompatibility groups.

N. Babudri

Papers

Expression of the plasmid pKM101-determined DNA repair system in recA − and lex − strains of Escherichia coli

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

6‐Methylangelicins: new monofunctional photochemotherapeutic agents for psoriasis

Restoration of mutability in non-mutable Escherichia coli carrying different plasmids.