Comparing the genotoxic sensitivities of human peripheral blood lymphocytes and mucosa cells of the upper aerodigestive tract using the Comet assay

Kleinsasser, Norbert; Wallner, Barbara C.; Kastenbauer, E.; Muenzenrieder, Ruth K.; Harréus, Ulrich

doi:10.1016/s1383-5718(00)00022-x

Cited by 37 publications

(14 citation statements)

References 17 publications

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“…Consequently, the group considered unstimulated mucosa cells from fresh biopsy samples. The use of mucosa cells has previously been described with only minor changes to original lymphocyte protocol (12) and has been published earlier (15,29).…”

Section: A B Discussionmentioning

confidence: 99%

“…Most studies on DRC are based on lymphocytes as the surrogate cell type (13,14 lymphocytes and upper aerodigestive tract epithelia, we included the two cell types in our investigations to further differentiate systemic and local effects (15). The aim of the study was to evaluate mutagen sensitivity and DRC in human lymphocytes and epithelial cells of the oropharynx of patients with and without squamous cell carcinoma (SCC) of the oropharynx.…”

Section: Introductionmentioning

confidence: 99%

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DNA repair and mutagen sensitivity of epithelial cells and lymphocytes in oropharyngeal cancer

et al. 2011

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Abstract. Tobacco-associated nitrosamines are known carcinogens causing DNA damage in epithelial cells of the head and neck. A matched case-control study was performed to evaluate the sensitivity of patients with squamous cell cancer (SCC) of the oropharynx, and controls to tobaccoassociated nitrosamines. Quantitative DNA repair was evaluated following a period of 15 and 30 min. Fresh biopsies from 100 male donors of macroscopically healthy oropharyngeal cells and lymphocytes (50 SCC patients and 50 controls) were incubated with N-nitrosodiethylamine (NDEA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) or N-nitrosonornicotine (NNN). DNA damage in epithelial cells and lymphocytes was assessed using the comet assay. Following incubation with NDEA, cells underwent a period of DNA repair. All of the nitrosamines caused equivalent genotoxic damage in mucosal cells and lymphocytes of the two groups. Lymphocyte DNA repair capacity in the control group (26.8 and 37.1% after 15 and 30 min) was comparable to the tumor group (23.6 and 40.6%). However, epithelial cell DNA repair capacity of carcinoma patients was significantly reduced to 17.1% (15 min) and 23% (30 min) compared to the DNA repair of the control group (36.2%, 15 min and 46.0%, 30 min). Mutagen sensitivity was comparable in patients and controls. Thus, reduced epithelial cell DNA repair capacity of tumor patients is a possible endogenous risk factor for the development of head and neck squamous cell cancer.

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Section: A B Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DNA repair and mutagen sensitivity of epithelial cells and lymphocytes in oropharyngeal cancer

et al. 2011

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“…Given the significant role of carcinogen exposure in these tumours, it proves difficult to study host factors related to cancer risk (Proia et al, 2006). Such studies are based on measurement of host DNA repair capacity, such as the bleomycin chromosome breakage assay (Wu et al, 1998;Rajaee-Behbahani et al, 2001), the host-cell reactivation assay (Diem and Runger, 1997), or the comet assay (Kleinsasser et al, 2000). These assays suggest host impairments in DNA repair, but they have found limited application in the clinical setting because they require intact cells, are labour intensive and may have limitations with respect to reproducibility (Berwick and Vineis, 2000).…”

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confidence: 99%

Microsatellite mutations in buccal cells are associated with aging and head and neck carcinoma

Slebos

Vadivelu

et al. 2008

Br J Cancer

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Carcinogen exposure from tobacco smoking is the major cause of upper aerodigestive tract cancer, yet heavy smokers only have about a 10% life-time risk of developing one of these cancers. Current technologies allow only limited prediction of cancer risk and there are no approved screening methods applicable to the general population. We developed a method to assess somatic mutational load using small-pool PCR (SP-PCR) and analysed mutations in DNA isolated from cells obtained by mouth rinse. Mutation levels in the hypermutable tetranucleotide marker D7S1482 were analysed in specimens from 25 head and neck squamous carcinoma (HNSCC) cases and 31 controls and tested for associations with age, smoking history and cancer status. We found a significant association between mutation frequency and age (P ¼ 0.021, Generalized Linear Model (GLM), N ¼ 56), but no influence of smoking history. Cases had higher mutation frequencies than controls when corrected for the effects of age, a difference that was statistically significant in the subgroup of 10 HNSCC patients who were treated with surgery only (P ¼ 0.017, GLM, N ¼ 41). We also present evidence that cancer status is linked to levels of nonunique, and presumably clonally derived, mutations in D7S1482. Insertion mutations were observed in 833 (79%) of 1058 alleles, of which 457 (43%) could be explained by insertion of a single repeat unit; deletion mutations were found in 225 (21%) of tested alleles.In conclusion, we demonstrate that the sensitive detection of single molecule mutations in clinical specimens is feasible by SP-PCR. Our study confirms an earlier report that microsatellite mutations increase with age and is the first to provide evidence that these mutations may be associated with cancer status in individual subjects.

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“…Kleinsasser et al reported, using an in vitro comet assay, that DNA damage (single-strand breaks) was signifi cantly induced by DIBP (354μmol/mL) in human oropharyngeal and nasal mucosa (32). In further work, Kleinsasser et al found that DIBP induced strand breaks in DNA, in both blood lymphocytes and normal mucosal cells from the oropharynx or larynx of patients of head and neck cancer (33).…”

Section: Discussionmentioning

confidence: 99%

Ovarian development in Wistar rat treated prenatally with single dose diisobutyl phthalate

Ray¹,

D’Souza²,

Kumar³

et al. 2013

BLL

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Abstract:Phthalates are a class of industrial compounds with an array of toxicological properties used in day to day life. Diisobutyl phthalate on (DIBP) is used as an additive to keep the plastics soft or fl exible (plasticizer) in nitrocellulose plastic, nail polish, explosives, lacquer manufacturing etc. Although DIBP exposure in humans is generally low, people in adhesive industries and pharmaceutical industries are exposed to higher levels. The aim of this study was to determine the effect of single dose of DIBP on developing ovary of Wistar rat. One hundred and eight adult pregnant Wistar rats were divided into control and experimental groups. Rats in experimental group were given DIBP on day 10, 12 and 14 of gestation at 0.375, 0.75 and 1.25 ml/kg body weight dose intraperitoneally in a single dose. Sections of ovaries collected on day 21 of gestation were stained with hematoxylin and eosin and examined and Masson's trichrome histologically. Sections belonging to the control group showed the presence of oocytes in clusters separated by thin fi brous septa. Degeneration oocytes, empty follicles surrounded by follicular cells without gonocytes in the center were observed in ovarian stroma. Blood vessels in the ovarian stroma were prominent and congested. Around a bunch of follicles total architectural disarray was observed although on special staining fi brosis was not evident. As pregnant women are constantly exposed, effect of DIBP on ovary of a developing fetus would denote the long term consequence in future generations (Fig. 5, Ref. 39 Phthalates are a class of widely used industrial compounds known technically as dialkyl or alkyl aryl esters of 1, 2-benzenedicarboxylic acid. The common forms of phthalates are Diethyl hexyl phthalate (DHEP), Diallyl phthalates (DAP), Di-n-propyl phthalates (DPP), Di-n-butyl phthalates (DBP), and Diisobutyl phthalates (DIBP).Phthalates with a variety of toxicological properties are used in day to day life. These phthalates are nearly omnipresent in modern society and are found in the plastic items, vinyl fl ooring, wall coverings, lubricants, adhesives, detergents, nail polish, hair spray and car wash (1).The adverse effects produced by phthalates are changes in morphology, physiology, growth, development or life span of an organism which results in an impairment of functional capacity and ability to compensate for additional stress (2). Diisobutyl phthalateDIBP (phthalic acid ,di isobutyl ester 1,2-benzenedicarboxylic acid ,bis-(2-methyl propyl) ester di-(isobutyl)-1,2-benzene dicarboxylate) is the branched isomer of DBP and an additive used to keep the plastics soft or more fl exible (plasticizer) often in combination with other phthalates. DIBP is used in nitrocellulose plastic, nail polish, explosive materials, lacquer manufacturing, consumer products, blood bags, pharmaceuticals and automobile parts. They are ubiquitous in our environment and most people including pregnant women and their fetuses are exposed to multiple phthalates at a time. Saillenfait et al estim...

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Comparing the genotoxic sensitivities of human peripheral blood lymphocytes and mucosa cells of the upper aerodigestive tract using the Comet assay

Cited by 37 publications

References 17 publications

DNA repair and mutagen sensitivity of epithelial cells and lymphocytes in oropharyngeal cancer

DNA repair and mutagen sensitivity of epithelial cells and lymphocytes in oropharyngeal cancer

Microsatellite mutations in buccal cells are associated with aging and head and neck carcinoma

Ovarian development in Wistar rat treated prenatally with single dose diisobutyl phthalate

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