In vitro DNA damage/alkaline elution assay for predicting carcinogenic potential

Swenberg, James A.; Petzold, Gary L.; Harbach, P.R.

doi:10.1016/s0006-291x(76)80100-3

Cited by 132 publications

(16 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two different types of approaches have been developed for monitoring different damage to DNA. First, indirect approaches such as the alkaline comet assay [12] or the alkaline elution technique [13] are very sensitive methods for measuring DNA strand breaks [9,14]. The alkaline single gel electrophoresis assay, particularly in its basal version, is not able to measure defined types of DNA damage since strand breaks thus measured may consist of frank nicks together with abasic sites and several alkali-labile oxidized bases.…”

Section: Introductionmentioning

confidence: 99%

Site-specific radical formation in DNA induced by Cu(II)–H2O2 oxidizing system, using ESR, immuno-spin trapping, LC-MS, and MS/MS

Bhattacharjee

Deterding

Chatterjee

et al. 2011

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Oxidative stress-related damage to the DNA macromolecule produces a multitude of lesions that are implicated in mutagenesis, carcinogenesis, reproductive cell death and aging. Many of these lesions have been studied and characterized by various techniques. Of the techniques that are available, the comet assay, HPLC-EC, GC-MS, HPLC-MS and especially HPLC-MS/MS remain the most widely used and have provided invaluable information on these lesions. However, accurate measurement of DNA damage has been a matter of debate. In particular, there have been reports of artifactual oxidation leading to erroneously high damage estimates. Further, most of these techniques measure the end product of a sequence of events and thus provide only limited information on the initial radical mechanism. We report here a qualitative measurement of DNA damage induced by a Cu(II)-H2O2 oxidizing system using immuno spin-trapping (IST) with EPR, MS and MS/MS. The radical generated is trapped by DMPO immediately upon formation. The DMPO adduct formed is initially EPR active but subsequently is oxidized to the stable nitrone, which can then be detected by IST and further characterized by MS and MS/MS.

show abstract

Section: Introductionmentioning

confidence: 99%

Site-specific radical formation in DNA induced by Cu(II)–H2O2 oxidizing system, using ESR, immuno-spin trapping, LC-MS, and MS/MS

Bhattacharjee

Deterding

Chatterjee

et al. 2011

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…In addition, chronic feeding studies of Captan in mice have demonstrated an induction of duodenal hyperplasia and tumor formation [Stauffer Chemical Company, 1985;Chevron Chemical Company, 19801. While the mechanism underlying these genotoxic effects is not known, several reports have suggested that Captan may interact with DNA [Anderson and Rosenkranz, 1974;Stauffer Chemical Company, 19811 and induce DNA repair [Swenberg et al, 1976;Ahmed et al, 1977;Simmon et al, 19771, but a systematic examination of this question has been lacking. This study was designed to examine the nature of the genotoxic events associated with Captan exposure to human cells.…”

Section: Introductionmentioning

confidence: 99%

Effects of captan on dna and dna metabolic processes in human diploid fibroblasts

Snyder¹

1992

Environ and Mol Mutagen

View full text Add to dashboard Cite

The fungicide Captan has been examined for its effects on DNA and DNA processing in order to better understand the genotoxicity associated with this agent. Captan treatment resulted in production of DNA single strand breaks and DNA-protein cross-links and elicited an excision repair response in human diploid fibroblasts. Captan was also shown to inhibit cellular DNA synthesis and to form stable adducts in herring sperm and human cellular DNA. Misincorporation of nucleotides into Captan-treated synthetic DNA templates was significantly elevated in an in vitro assay using E. coli DNA polymerase I, suggesting that DNA adduct formation by Captan could have mutagenic consequences. In sum, these studies demonstrate that Captan is capable of interacting with DNA at a number of levels and that these interactions could provide the basis for Captan's genotoxicity. The extreme cytotoxicity of this fungicide, however, could be due to other cellular effects since at the IC50 for cell killing, approximately 0.8 microM, none of the above genotoxic events could be detected by the methods employed.

show abstract

“…Chinese hamster lung fibroblast V79 Cells Up to 10 mM (1494 µg/ml) (control + 9 doses tested) Negative (±S9) (Swenberg et al, 1976) Isomer not specified. Well conducted study.…”

Section: Chromosomal Aberration Assaymentioning

confidence: 99%

Flavouring Group Evaluation 26: Amino acids from chemical group 34

2010

EFSA Journal

View full text Add to dashboard Cite

The present Flavouring Group Evaluation deals with five amino acids.Three of the five flavouring substances possess one chiral centre and two possess two chiral centres.One of the substances is the naturally occurring L-amino acid, L-cystine .006], and another is the hydrochloride salt of a naturally occurring L-amino acid, 1-lysine monochlorhydrate ], for which the Panel concluded that the use of the Procedure was inappropriate, as the human exposures to L-cystine and L-lysine through food are orders of magnitude higher than the anticipated levels of exposure from the use as flavouring substances. Therefore, the flavouring substance L-cystine and l-lysine monochlorhydrate are not taken through the Procedure. However, the Panel concluded that the substances were not of safety concern at their estimated levels of intake as flavouring substances. The other three substances in this flavouring group are evaluated as racemates and are taken through the Procedure.The five flavouring substances are classified into structural class I.In its evaluation, the Scientific Panel as a default used the Maximised Survey-derived Daily Intakes (MSDIs) approach to estimate the per capita intakes of the flavouring substances in Europe. However, when the Scientific Panel examined the information provided by the European flavouring industry on the use levels in various foods, it appeared obvious that the MSDI approach in a number of cases would grossly underestimate the intake by regular consumers of products flavoured at the use level reported by the industry, especially in those cases where the annual production values were reported to be small. In consequence, the Scientific Panel had reservations about the data on use and use levels provided and the intake estimates obtained by the MSDI approach. In the absence of more precise information that would enable the Scientific Panel to make a more realistic estimate of the intakes of the flavouring substances, the Scientific Panel has decided also to perform an estimate of the daily intakes per person using a modified Theoretical Added Maximum Daily Intake (mTAMDI) approach based on the normal use levels reported by industry. In those cases where the mTAMDI approach indicated that the intake of a flavouring substance might exceed its corresponding threshold of concern, the Scientific Panel decided not to carry out a formal safety assessment using the Procedure. In these cases the Scientific Panel requires more precise data on use and use levels.According to the default MSDI approach, the five flavouring substances in this group have intakes in Europe from 0.12 to 30 microgram/capita/day which are below the threshold of concern value for structural class I (1800 microgram/person/day) substances.The human exposure of the candidate substance L-cystine .006] and l-Lysine from the candidate substance l-lysine monochlorhydrate .031] through food is orders of magnitude higher than the anticipated levels of exposure from the use of the flavouring substances. Therefore the two substances are not...

show abstract

In vitro DNA damage/alkaline elution assay for predicting carcinogenic potential

Cited by 132 publications

References 5 publications

Site-specific radical formation in DNA induced by Cu(II)–H2O2 oxidizing system, using ESR, immuno-spin trapping, LC-MS, and MS/MS

Site-specific radical formation in DNA induced by Cu(II)–H2O2 oxidizing system, using ESR, immuno-spin trapping, LC-MS, and MS/MS

Effects of captan on dna and dna metabolic processes in human diploid fibroblasts

Flavouring Group Evaluation 26: Amino acids from chemical group 34

Contact Info

Product

Resources

About