Genetic toxicity assessment: employing the best science for human safety evaluation part III: the comet assay as an alternative to in vitro clastogenicity tests for early drug candidate selection.

Early screening of drug candidates for genotoxicity typically includes an analysis for mutagenicity in bacteria and for clastogenicity in cultured mammalian cells. In addition, in recent years, an early assessment of photogenotoxicity potential has become increasingly important. Also, for screening purposes, expert computer systems can be used to identify structural alerts.

Comparative study with the alkaline Comet assay and the chromosome aberration test.

The alkaline Comet assay is becoming a useful tool for early genotoxicity testing of new pharmaceutical drug candidates. The aim of this study was to elucidate the predictive value of Comet assay results for the outcome of the chromosome aberration (CA) test. For this purpose, a validation exercise with 13 drug candidates was carried out utilizing V79 Chinese hamster cells and human lymphocytes.

Biomarkers of genetic damage and inflammation in blood and bronchoalveolar lavage fluid among former German uranium miners: a pilot study.

Former East German uranium miners who are known to have been exposed to radon are estimated to be at high risk for lung carcinogenesis. Among these miners over 200 occupationally caused lung cancer cases are expected to occur each year, resulting in a total of 7,000-24,000 excess lung cancer cases in the coming years. It is still unknown whether there is a correlation between biomarkers and the exposure of the uranium miners to ionizing radiation that might enable us to trace those miners with high lung cancer risk.

DNA damage in human leukocytes after ischemia/reperfusion injury.

Leukocytes have been shown to play an important role in the development of tissue injury after ischemia and reperfusion (I/R). In the present study, the effects of tourniquet-ischemia on induction of DNA damage in peripheral leukocytes and on respiratory burst of neutrophils in humans were examined. The DNA damage was measured as increased migration of DNA using the single-cell gel-electrophoresis technique (comet assay).

Laser pyrolysis products-genotoxic, clastogenic and mutagenic effects of the particulate aerosol fractions.

Laser therapy has gained wide acceptance and application in many medical disciplines. Nevertheless, during surgical procedures, the thermal destruction of tissue creates a smoke plume. Recent research data indicate that pyrolysates liberated during vaporisation of tissue induce DNA damage.

Laser pyrolysis products: sampling procedures, cytotoxic and genotoxic effects.

The use of lasers in medical applications has grown enormously in the last few years. Recent chemical analysis of the laser pyrolysis products revealed that aerosols generated by pyrolytic decomposition of tissue could be health hazards. Therefore we analysed the genotoxic and mutagenic effects of laser pyrolysis products from different types of porcine tissue.

Short-term effects of early-acting and multilineage hematopoietic growth factors on the repair and proliferation of irradiated pure cord blood (CB) CD34+ hematopoietic progenitor cells.

Purpose: Hematopoietic growth factor(s) (GF) may exert positive effects in vitro or in vivo on the survival of hematopoietic stem and progenitor cells after accidental or therapeutic total body irradiation.

Methods And Materials: We studied the clonogenic survival and DNA repair of irradiated (0.36, 0.

[[Systemic genotoxic effect caused by ischemia-/reperfusion-/surgical trauma of the lower extremity--detection of DNA chain breaks in leukocytes with the Comet Assay]].

Ischemia-reperfusion-injury (IRI) represents a fundamental common pathway of tissue damage in a wide variety of disease processes, i.e. myocardial infarction, septic or hemorrhagic shock, multiple organ failure, trauma and organ transplantation.

Changes in the repair capacity of blood cells as a biomarker for chronic low-dose exposure to ionizing radiation.

The purpose of this study was to examine whether changes in the repair capacity of blood cells could be used as a valuable biomarker for radiation exposure. To characterize the repair kinetics in nonirradiated and irradiated cells we first performed in vitro split dose experiments. DNA damage and DNA repair capacity were analysed using the comet assay.

Radiation-induced DNA damage in canine hemopoietic cells and stromal cells as measured by the comet assay.

Stromal cell progenitors (fibroblastoid colony-forming unit; CFU-Fs) are representative of the progenitor cell population of the hemopoietic microenvironment in bone marrow (BM). Previous studies of the radiation dose-effect relationships for colony formation have shown that canine CFU-Fs are relatively radioresistant as characterized by a D0 value of about 2.4 Gy.

DNA-damage detection in man after radiation exposure--the comet assay--its possible application for human biomonitoring.

The exposure of human beings to ionizing radiation is still of great concern to occupational and environmental medicine. The goal of this workshop is to identify a panel of biological markers that could be used in humans after exposure to ionizing radiation. The comet assay or single cell gel (SCG) assay is a new method that allows efficient determination of single-strand breaks (SSB) and double-strand breaks (DSB), as well as alkali-labile sites in the DNA of single cells.

Does physical activity induce DNA damage?

The single cell gel electrophoresis (SCG) assay (comet assay) is a sensitive technique for detecting the presence of DNA strand-breaks and alkali-labile damage in individual cells. This technique was used to study peripheral blood cells from three volunteers after physical activity. The test subjects had to run on a treadmill and were checked for blood pressure and ECG, lactate concentration and creatine kinase activity.

Early effects of benzene exposure in mice. Hematological versus genotoxic effects.

Female BDF1 mice were exposed to 100, 300 and 900 ppm benzene 6 h/day, 5 days/week, up to 8 weeks. Hematological studies included peripheral blood data, T4 and T8 lymphocyte counts in the blood and the spleen, hemopoietic stem and progenitor cell assays in the marrow (CFU-S, CFU-C, BFU-E, CFU-E). The single cell gel assay ("comet assay") was applied in parallel with cells from the peripheral blood, bone marrow, spleen and liver.

Reduction of benzene toxicity by toluene.

BDF1 mice were exposed in inhalation chambers to benzene (900 ppm, 300 ppm) and/or toluene (500 ppm, 250 ppm) 6 hr per day, 5 days per week, for up to 8 weeks. Benzene alone induced a slight anemia after 4 and 8 weeks and a reduction of BFU-E and CFU-E numbers in the marrow. The coexposure to toluene reduced the degree of anemia.