Increased Yield of Residual γH2AX Foci in p53-Deficient Human Lung Carcinoma Cells Exposed to Subpicosecond Beams of Accelerated Electrons.

We studied quantitative yield of residual (24 h post-irradiation) phosphorylated histone (γH2AX) foci as a marker of DNA double strand breaks in wild-type A549 and p53-deficient H1299 human lung carcinoma cells after exposure to subpicosecond (energy 4 MeV, pulse duration 400 fsec, peak dose rate during the pulse 16 GGy/s) and quasi-continuous (energy 3.6 MeV) beams of accelerated electrons in a dose range of 0.5-10.0 Gy. The efficiency of pulse irradiation in A549 and H1299 cells assessed by the yield of residual foci was higher than the efficiency of quasi-continuous exposure by 1.8 and 5.3 times, respectively. Significant differences in quantitative yield of residual γH2AX foci between wild-type and p53-deficient cell lines were observed only after exposure to subpicosecond, but not quasi-continuous beams of accelerated electrons.

The incidence of various types of childhood leukemia in Armenia (1991-2002).

PURPOSE: To analyse the incidence of various types of childhood leukemia in Armenia for the period 1991-2002. MATERIALS AND METHODS: The results presented in this communication were based on the official data obtained from the Center of Haematology, Yerevan, Armenia, where all patients with leukemia are diagnosed and treated. The types of leukemia were classified according to ICD-10; C91.0 - acute lymphoid leukemia (ALL), C91.1 - acute myeloid leukemia (AML) and C92.0 - chronic myeloid leukemia (CML). RESULTS: There was a substantial prevalence of ALL among all cases (85.6%, mean value for 12 years). ALL varied from 74.4% in 1998 to 95.4% in 1992. The mean percentage of AML and CML were 12.3 and 2.1, respectively. The proportion of ALL/AML + CML in Armenian children varied from 20.5 in 1992 to 3.2 in 1998 with a mean value of 7.2. There was not any regularity in various leukemia types in children during the observed period of time. CONCLUSION: No regularity in the incidence of various childhood leukemia types was revealed during 1991-2002. Like in most countries, a substantial prevalence of ALL incidence was observed.

Chromosome aberrations in lymphocytes of persons exposed to an earthquake in Armenia.

OBJECTIVE: This study attempted to determine the level of chromosome aberrations in lymphocytes of victims of the 1988 earthquake in Armenia. METHODS: Chromosome aberrations were measured in blood samples taken from 41 victims of the earthquake that hit Armenia in 1988 and in samples of 47 reference blood donors. The victims suffered from severe psychoemotional stress but were otherwise healthy. All the samples were taken 2 to 3 weeks after the earthquake. All the subjects were lifetime nonsmokers. The cells were scored blind as to the exposure status. RESULTS: The subjects exposed to the earthquake had a higher proportion of cells with chromosome aberrations [3.1 (SD 2.1)%] than the referents [1.7 (SD 1.3)%, P-value for the difference 0.0009]. The difference persisted when the values were adjusted for age and gender [relative risk (RR) 1.9, 95% confidence interval (95% CI) 1.4-2.5]. The difference was present for double breaks (RR 4.1, 95% CI 2.6-6.4), but not for single breaks (RR 1.1, 95% CI 0.8-1.7). The exposed subjects also had a lower percentage of cells with 46 chromosomes (P=0.03) than the referents. CONCLUSIONS: This study suggests an increase in chromosome aberrations in the lymphocytes of victims of a severe earthquake as compared with the levels of referents. If not due to bias or confounding, the difference may reflect the effect of either environmental exposures related to the earthquake or severe psychogenic stress. The levels of chromosome aberrations found among the earthquake victims in this study are comparable with those found in prospective studies of long-term cancer risk.

In situ monitoring of the ambient air around the chloroprene rubber industrial plant using the Tradescantia-stamen-hair mutation assay.

The city of Yerevan, the capital of Armenia, has been one of the heavily polluted cities since the earlier USSR era. A Chloroprene Rubber Industrial Plant has been the major contributor of air pollution in this city. The first attempt has been undertaken to detect the mutagenic effect of the ambient air around this industrial complex using the Tradescantia-stamen-hair-mutation (Trad-SHM) assay. Tradescantia clone 02 was used for this study. Pots of Tradescantia plants were exposed to ambient air in 10 different locations around the industrial establishment during the months of May and June, 1991 and 1992. Three series of in situ monitoring experiments were carried out. In the first series, sites numbers 1 through 4 were located in the industrial complex, and the second series, sites numbers 5 through 7 were located 1.0-1.3 km away from the Rubber Plant and the third series, sites numbers 8 though 10 were situated 1.5 km from the chemical plant and the monitoring plants were elevated at 5, 13, and 32 m above ground. A control group of plants were grown in a greenhouse about 13 km away from the polluted air from the chemical plant. Results of these two consecutive year's study show significantly elevated high levels of pink mutation events (PME) over the control at sites 1, 2, and 4 in the first series of the study. Positive responses were observed at all sites in the second series of the study. Only site 8 (June 1991) in the third series of the study was significantly higher in PME over the control.

The comparative clastogenic activity of mainstream tobacco smoke from cigarettes widely consumed in Armenia.

Whole-body exposure of male albino Swiss mice to the mainstream smoke produced by 10 types of cigarettes widely consumed in Armenia resulted in a significant increase (2.4-5.6-fold) of the number of micronucleated bone marrow polychromatic erythrocytes. The smoke produced by cigarettes manufactured in Armenia, Russia and Bulgaria was more clastogenic than the smoke produced by cigarettes manufactured in the USA. A high direct correlation was observed between the number of micronucleated polychromatic erythrocytes and the content of tar and nicotine.

Comparative investigation of anticlastogenic effects in cell cultures of healthy donors and patients with nettle-rash.

In cultures of lymphocytes from 12 healthy donors and 12 patients with nettle-rash (NR) the anticlastogenic effect of the antimutagens WR-2721 (WR), bemitil (BM), tomerzol (TM) and interferon (IF) on the induction of chromosomal aberrations by photrin (PT) and dioxidine (DX) was investigated. There were no statistically significant differences between healthy donors and patients with NR in the levels of chromosomal aberrations that were spontaneous or induced by PT or DX. Statistically significant protective effects of BM, WR, TM and IF were demonstrated in cells of healthy donors after treatment with PT or DX, and after modification of the clastogenic action of PT in lymphocytes of NR patients. There was no protective effect of any of the anticlastogens after treatment of the lymphocyte cultures from NR patients with DX. That observation allows us to suggest the test of anticlastogenic action as a measure of sensitivity of the chromosomal apparatus in groups with different genetic risks.

Similar defects in DNA repair and replication in the pigmented xerodermoid and the xeroderma pigmentosum variants.

The "pigmented xerodermoid" was previously defined on the basis of mild clinical symptoms that suggested it might be similar to but distinct from xeroderma pigmentosum (XP). XP and pigmented xerodermoid cell cultures were irradiated with ultraviolet light and unscheduled DNA synthesis, strand breakage during repair, chain growth during semiconservative DNA replication with or without caffeine, and the recovery of DNA replication were determined. It is concluded that a pigmented xerodermoid cell culture is indistinguishable from the XP variant and the former term is therefore redundant. The defect common to these cell types appears to be the loss of a gene product that permits normal cells to replicate DNA without interruption at damaged sites (u.v.-induced pyrimidine dimers). The consequence of this loss is that replication forks are blocked more frequently and at lower doses in XP variant cells. The correlation between this defect and high levels of actinic carcinogenesis in these patients points to an important role for perturbations in DNA replication in human carcinogenesis.