Chromosome sensitivity to bleomycin-induced mutagenesis in lymphocytes from colorectal cancer patients under 40 years of age

Fireman, Zvi; Shabtai, Fiorella; Lurie, B.

doi:10.1007/bf02257804

Cited by 12 publications

(13 citation statements)

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“…Patients with colorectal cancers from different sites have different mutagen sensitivities; this has been shown by Fireman et al 11. In our study, left sided colon cancer patients show higher mutagen sensitivity than those with right sided cancer (table 4).…”

Section: Discussionsupporting

confidence: 78%

Mutagen sensitivity and p53 expression in colorectal cancer in China

Shao

Lai

Huang

2001

Postgraduate Medical Journal

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Objective-This study was designed to investigate DNA damage and/or repair capability, non-random chromatid breakage, and p53 expression in patients with colorectal cancer. Methods-The bleomycin sensitivity assay was used in a case-control study to compare the DNA damage repair system between colorectal cancer patients and controls. G-banding was used to search for non-random chromatid breaks. Immunocytochemistry was used to investigate p53 expression in tumour tissues and adjacent normal tissues. Results-It was found that cases typically had a higher number of chromosome breaks than controls (0.84 v 0.69 breaks/ cell, p<0.01). After correction by sex and age, the diVerence was still significant (F=4.38, p<0.05). The correlation coefficient between mutagen sensitivity and age was 0.31(p<0.05) in controls and 0.18 (p>0.05) in cases. The ratio of odds ratios among bleomycin resistant, sensitive, and hypersensitive classes was 1:2.31:3.85. Overexpression of p53 was detected in 25 of 47 tumour tissues independent of tumour stage. Cases who had a family history of cancer were susceptible to the p53 aberration (p<0.05). Chromosomes 1p, 5q, and 14q were susceptible to breakage in patients with colorectal cancer. Conclusion-Patients with colorectal cancer show increased bleomycin induced chromatid breaks and may have minor DNA repair deficiencies. p53 aberration is an early event in the development of colorectal cancer, but no definite correlation is found between p53 overexpression and mutagen sensitivity. (Postgrad Med J 2001;77:713-716)

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Section: Discussionsupporting

confidence: 78%

Mutagen sensitivity and p53 expression in colorectal cancer in China

Shao

Lai

Huang

2001

Postgraduate Medical Journal

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“…As shown in Figure 1, lungs from animals receiving endotoxin had extensive infiltration of MPO-positive cells, most prominently at 45 minutes after administering endotoxin [23]. The marked alteration in lung architecture was largely resolved by 135 min after endotoxin.…”

Section: Resultsmentioning

confidence: 99%

“…We have previously described an ex-vivo perfusing piglet preparation, which permits perfusion restricted to the lung and the liver using autologous blood [23]. Piglets were anesthetized, a tracheostomy was performed, and cannulas were placed in a carotid artery and a jugular vein.…”

Section: Methodsmentioning

confidence: 99%

Infusion of freshly isolated autologous bone marrow derived mononuclear cells prevents endotoxin-induced lung injury in an ex-vivo perfused swine model

et al. 2013

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IntroductionThe acute respiratory distress syndrome (ARDS), affects up to 150,000 patients per year in the United States. We and other groups have demonstrated that bone marrow derived mesenchymal stromal stem cells prevent ARDS induced by systemic and local administration of endotoxin (lipopolysaccharide (LPS)) in mice.MethodsA study was undertaken to determine the effects of the diverse populations of bone marrow derived cells on the pathophysiology of ARDS, using a unique ex-vivo swine preparation, in which only the ventilated lung and the liver are perfused with autologous blood. Six experimental groups were designated as: 1) endotoxin alone, 2) endotoxin + total fresh whole bone marrow nuclear cells (BMC), 3) endotoxin + non-hematopoietic bone marrow cells (CD45 neg), 4) endotoxin + hematopoietic bone marrow cells (CD45 positive), 5) endotoxin + buffy coat and 6) endotoxin + in vitro expanded swine CD45 negative adherent allogeneic bone marrow cells (cultured CD45neg). We measured at different levels the biological consequences of the infusion of the different subsets of cells. The measured parameters were: pulmonary vascular resistance (PVR), gas exchange (PO2), lung edema (lung wet/dry weight), gene expression and serum concentrations of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6.ResultsInfusion of freshly purified autologous total BMCs, as well as non-hematopoietic CD45(-) bone marrow cells significantly reduced endotoxin-induced pulmonary hypertension and hypoxemia and reduced the lung edema. Also, in the groups that received BMCs and cultured CD45neg we observed a decrease in the levels of IL-1β and TNF-α in plasma. Infusion of hematopoietic CD45(+) bone marrow cells or peripheral blood buffy coat cells did not protect against LPS-induced lung injury.ConclusionsWe conclude that infusion of freshly isolated autologous whole bone marrow cells and the subset of non-hematopoietic cells can suppress the acute humoral and physiologic responses induced by endotoxemia by modulating the inflammatory response, mechanisms that do not involve engraftment or trans-differentiation of the cells. These observations may have important implications for the design of future cell therapies for ARDS.

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“…The mutagen sensitivity assay was developed by Dr. T. C. Hsu (12) to score the number of bleomycin-induced chromatid breaks per cell in cultured primary peripheral blood lymphocytes and has been shown to provide a useful biomarker for susceptibility to different types of cancer, including those of the thyroid, upper aerodigestive tract, lung, colon, and head and neck (12)(13)(14)(15)(16)(17). In a pilot study of SCCHN (9), we used a modified assay with BPDE as the test mutagen, an ultimate tobacco metabolite etiologically related to SCCHN.…”

Section: Introductionmentioning

confidence: 99%

Chromosome Instability and Risk of Squamous Cell Carcinomas of Head and Neck

Wang¹,

Xiong²,

Zhao³

et al. 2008

Cancer Research

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In 895 subjects with squamous cell carcinoma of the head and neck (SCCHN) and 898 cancer-free controls matched by age, sex, and ethnicity, we validated our previous finding that mutagen sensitivity as measured by the frequency of chromatid breaks in vitro induced by benzo[a]pyrene diol epoxide (BPDE) is an independent risk factor for SCCHN. Using a previously established concentration of 4 Mmol/L BPDE to treat short-term cultured primary lymphocytes for 5 hours, we evaluated chromatid breaks in 50 well-spread metaphases for each blood sample. The mean frequency of BPDE-induced chromatid breaks was significantly higher in cases than in controls in non-Hispanic Whites (P = 0.0003) but not in other ethnic groups (P = 0.549 for Hispanic Americans and 0.257 for African Americans). The odds ratio associated with risk of SCCHN for the frequency of chromatid breaks greater than median value of controls was 1.56 (95% confidence interval, 1.27-1.91) in non-Hispanic Whites (767 cases and 763 controls) after adjustment for age, sex, smoking status, and drinking status. When the quartiles of the controls were used as the cutoff values, there was a dose response between the degree of mutagen sensitivity and risk of SCCHN in nonHispanic Whites (P trend = 0.0001). However, none of these associations in non-Hispanic Whites was identified in Hispanic Americans (69 cases and 70 controls) or African Americans (59 cases and 65 controls), possibly because of the small samples of these ethnic groups or ethnic difference in genetic variation, which needs to be confirmed in future studies.

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Chromosome sensitivity to bleomycin-induced mutagenesis in lymphocytes from colorectal cancer patients under 40 years of age

Cited by 12 publications

References 12 publications

Mutagen sensitivity and p53 expression in colorectal cancer in China

Mutagen sensitivity and p53 expression in colorectal cancer in China

Infusion of freshly isolated autologous bone marrow derived mononuclear cells prevents endotoxin-induced lung injury in an ex-vivo perfused swine model

Chromosome Instability and Risk of Squamous Cell Carcinomas of Head and Neck

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