Mutation induction and killing of Escherichia coli by DNA adducts and crosslinks: A photobiological study with 8-methoxypsoralen

Bridges, B.A.; Mottershead, R.P.; Knowles, Aileen F.

doi:10.1016/0009-2797(79)90127-3

Cited by 70 publications

(15 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Psoralens are light-activated carcinogens that, in the presence of near-UV light, make monoadducts to thymine and interstrand crosslinks (with the exception of angelicin) in the presence of an adjacent thymine in the opposite strand (31,32), as is the case with hisG428. In the present study, psoralen, 5-methoxypsoralen, and 8-methoxypsoralen (derivatives capable of crosslinking DNA) were considerably more mutagenic than angelicin in a UvrB+ background, suggesting that the formation ofinterstrand crosslinks is the major mutagenic lesion induced, as was previously suggested (23,32). The psoralens and mitomycin C (a quinone that causes crosslinks in DNA) required a UvrB+ background for mutagenic activity, which was one of the reasons for introducing TA102 (which is UvrB+) as a new tester strain.…”

Section: Discussionsupporting

confidence: 60%

“…TA104 is somewhat more sensitive than TA96 to reversion by all of the mutagens in Table 1 that reverted TA96 (data not shown). However, malondialdehyde is detected better (116 revertants per mg; 15 spontaneous revertants) by hisD6580 than by hisG428.. Crosslinking agents such as the psoralens and mitomycin C are lethal to uvrB strains (23,24) and therefore, were not detected as mutagens by either TA96 or TA104.…”

Section: Selection Of Hisg428 a Mutation Reverted By Chemicalmentioning

confidence: 99%

See 1 more Smart Citation

A new Salmonella tester strain (TA102) with A X T base pairs at the site of mutation detects oxidative mutagens.

Levin¹,

Hollstein²,

Christman³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

587

262

View full text Add to dashboard Cite

A new tester strain, TA102, is described as an addition to the set of strains for the Salmonella/microsome mutagenicity test. This strain contains A-T base pairs at the site of the mutation (determined by DNA sequence analysis) in contrast to the other Salmonella tester strains that detect mutagens damaging G-C base pairs. This strain differs from previous tester strains in that the mutation has been introduced into a multicopy plasmid, so that -30 copies of the mutant gene are available for back mutation. The new strain detects a variety of oxidative mutagens, including x-rays, bleomycin, hydrogen peroxide and other hydroperoxides, streptonigrin and other quinones, and phenylhydrazine; a variety of aldehydes, including formaldehyde, glyoxal, kethoxal, glutaraldehyde, and malondialdehyde; a number of psoralens (in the presence of near-UV light), mitomycin C, neocarzinostatin, and UVlight. Some ofthese mutagens have been previously shown to damage thymine in DNA. Several auxiliary tester strains also are described, including TA96, a frameshift tester strain with a hot spot for mutation at a run of five A-T base pairs with a specificity similar to that of TA102. The importance of oxidative mutagens is discussed.Damage to DNA is likely to be a major cause ofcancer and other diseases (1, 2). The Salmonella mutagenicity test (3), along with other short-term assays (4), is being extensively used to survey a variety of substances in our environment for mutagenic activity. The test measures back-mutation in several specially constructed mutants of Salmonella. A homogenate of rat liver (or other mammalian tissue) is added to the bacterial suspension as an approximation ofmammalian metabolism (3). By using this system, over 80% of the organic carcinogens tested have been detected as mutagens (5-7).All of the histidine-requiring mutants in the standard set of Salmonella tester strains have G-C base pairs at the critical site for reversion: -C-C-C-in the base-pair substitution strain TA100,* -C-C-C-C-C-C-in the frameshift strain TA97 (8), and -C-G-C-G-C-G-C-G-in the frameshift tester strain TA98 (9). The present study describes tester strains that have A-T base pairs at the critical site for reversion. These strains detect a variety of oxidants and other agents as mutagens which were not detected in the standard tester strains. Cloning and Sequence Analysis of hisG428. The ochre mutation, hisG428 (11), was cloned by in vivo recombination into a derivative of phage M13Hol76 carrying the hisD6610 mutation (8). M13Hol76 contains the histidine operator, G, D, and part of the C genes from Salmonella. The male derivative of hisG428, TA2894, was infected with M13Hol76hisD6610 and recombinant phage were selected by their ability to complement the hisA(D)2121 deletion host, TA2891, and the inability to complement the hisA(G)8476 deletion host, TA2892. Singlestranded DNA from this HisD+ HisG-recombinant phage was isolated (12) and subjected to sequence analysis (13). MATERIALS AND METHODSPlasmid pAQl. M13Hol76hisG428 DNA was...

show abstract

Section: Discussionsupporting

confidence: 60%

Section: Selection Of Hisg428 a Mutation Reverted By Chemicalmentioning

confidence: 99%

A new Salmonella tester strain (TA102) with A X T base pairs at the site of mutation detects oxidative mutagens.

Levin¹,

Hollstein²,

Christman³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

587

262

View full text Add to dashboard Cite

show abstract

“…Two groups (6, 7) also found 8-methoxypsoraleninduced mutations in Uvr-cells, but when the cells were reirradiated with NUV to convert monoadducts to crosslinks, the yield of mutations decreased. Since cell survival also decreased upon reirradiation, it was concluded that crosslinks were lethal but not mutagenic in E. coli (6,7). Now, it is apparent that crosslinks are mutagenic, but apparently only in Uvr+ cells.…”

Section: Resultsmentioning

confidence: 99%

“…It has been apparent for some time that psoralen/NUV treatments producing both crosslinks and monoadducts induce mutations in E. coli (4)(5)(6)(7)(8). However, it was only recently that crosslinks alone were proven to be mutagenic and not just lethal.…”

mentioning

confidence: 99%

Incision by UvrABC excinuclease is a step in the path to mutagenesis by psoralen crosslinks in Escherichia coli.

Sladek

Melian

Howard-Flanders

1989

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

ABSTRACT4,5',8-Trimethylpsoralen (psoralen) plus near UV light produces interstrand crosslinks and monoadducts in DNA, both ofwhich are mutagenic. InEscherichia coil, crosslinks are incised by UvrABC excinuclease, an event that can lead to homologous recombination and repair. To determine whether UvrABC incision of crosslinks is a step in the path to mutagenesis as well as repair, the effect of DNA homologous to a target gene on a plasmid was determined. pSV2-gpt DNA was treated with psoralen and transformed into a pair of hosts: one was gpt', the other was A(gpt-ac)5. The DNA was extracted and transformed into a tester strain

show abstract

“…If the mechanism of incision-excision of the initial adduct in a crosslink requires polymerization of the opposite strand as a template, either polymerization would have to be error prone or additional protein factors may be required in the process of cross-link repair. There is evidence that cross-link repair is a mutagenic process (146,147) suggesting that aberrant polymerization reactions under certain conditions may be a necessary consequence of a polymerasecoordinated excision reaction. There is, in addition, a suggestion that the recA protein may serve in an auxiliary capacity for excision of the cross-linked region (146,147).…”

Section: H Implications Of a Uvr-multiprotein Dna Complexmentioning

confidence: 99%

Phosphodiesterases Involved in DNA Repair

Weiss

Grossman

1987

Advances in Enzymology - And Related Areas of Molecular Biology

View full text Add to dashboard Cite

Mutation induction and killing of Escherichia coli by DNA adducts and crosslinks: A photobiological study with 8-methoxypsoralen

Cited by 70 publications

References 16 publications

A new Salmonella tester strain (TA102) with A X T base pairs at the site of mutation detects oxidative mutagens.

A new Salmonella tester strain (TA102) with A X T base pairs at the site of mutation detects oxidative mutagens.

Incision by UvrABC excinuclease is a step in the path to mutagenesis by psoralen crosslinks in Escherichia coli.

Phosphodiesterases Involved in DNA Repair

Contact Info

Product

Resources

About