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Currently, our knowledge of how different cell types in a tissue microenvironment respond to low and high linear energy transfer (LET) radiation is highly restricted. In this study, a comparative analysis was performed on γ-ray-induced DNA damage and repair in primary human melanocytes and keratinocytes isolated from 3 donors. Our study demonstrates a modest interindividual variability in both melanocytes and keratinocytes in terms of both spontaneous and ionizing radiation (IR)-induced 53BP1 foci formation and persistence. Melanocytes, in general, showed a slightly elevated (1.66–2.79 folds more) 53BP1 foci induction relative to keratinocytes after exposure to different doses of γ-rays (0.1–2.5 Gy) radiation. To verify the influence of ATM kinase on IR-induced 53BP1 foci formation, melanocytes and keratinocytes were treated with a specific ATM kinase inhibitor (KU55993, 10 μM) for 1 h prior to radiation. ATM kinase inhibition resulted in the reduction of both spontaneous and IR-induced 53BP1 foci by 17–42% in both melanocytes and keratinocytes of all the 3 donors. Increased persistence of IR-induced 53BP1 foci number was observed in ATM-inhibited melanocytes and keratinocytes after different post exposure times (6 h and 24 h). Taken together, our study suggests that interindividual variations exist in the induction and repair of DNA double-strand breaks (DSBs) in melanocytes and keratinocytes and that ATM is crucial for an optimal DSB repair efficiency in both human skin cell types. [ABSTRACT FROM AUTHOR]

Methylation of cytosine is a common biological process both in prokaryotic and eukaryotic cells. In addition to 5-methylcytosine (5mC), some bacterial species contain in their genome N4-methylcytosine (N4mC). Methylation at C5 has been shown to enhance the formation of pyrimidine dimeric photoproducts but nothing is known of the effect of N4 methylation on UV-induced DNA damage. In the present work, we compared the yield and the nature of bipyrimidine photoproducts induced in a series of trinucleotides exhibiting a TXG sequence where X is either T, C, 5mC or N4mC. HPLC associated to tandem mass spectrometry was used to quantify cyclobutane pyrimidine dimers (CPD), (6-4) photoproducts (64PP) and their Dewar valence isomer. Methylation at position N4 was found to drastically increase the reactivity of C upon exposure to both UVC and UVB and to favor the formation of 64PP. In contrast methylation at C5 increased the yield of CPD at the expense of 64PP. In addition, enhancement of photoreactivity by C5 methylation was much higher in the UVB than in the UVC range. These results show the drastic effect of the methylation site on the photochemistry of cytosine. [ABSTRACT FROM AUTHOR]

We investigated the interactions between ozone-depleted air masses and subsequent changes in UVB on marine bacterial abundance and production at Palmer Station, Antarctica from September to November 1999. During periods of low total column ozone (TCO), bacterial cell concentrations declined by 57%. Photoinhibition of bacterial [3H]-leucine (Leu) and [3H]-thymidine (TdR) incorporation due to UVB was greatest during periods of low TCO in September and early October. During diel (∼28 h) exposure experiments, light treatment samples exhibited >75–100% inhibition of TdR incorporation by mid-afternoon. Leu incorporation exhibited maximum inhibition (50–100%) at sunset and early evening hours. Leu and TdR incorporation in light treatment samples did not exhibit recovery during subsequent periods of darkness. Bacterial Leu and TdR incorporation rates were inversely related to Setlow Dose during a period of recovery from low TCO. These data further suggested a threshold exposure below which bacterial Leu and TdR incorporation recovered rapidly. Recovery of bacterial production after acute Setlow Dose exposures lagged recovery of TCO and was linearly related to TCO measured 2 days previously. This lag in recovery may have resulted from the energetically expensive repair of UVR-induced DNA damage acquired during periods of low TCO. [ABSTRACT FROM AUTHOR]

Inorganic arsenic (arsenate and arsenite) are well known human carcinogens. Apoptosis is a normal biological process that is involved in regulating cell development and differentiation, and is an important protective response to cell injury. The aim of this study was to determine the long term arsenic effect on human small airway epithelial cells (SAEC) by analyzing two distinct apoptosis-inducing agents, Fas ligand (Fas L), which evokes death receptor-mediated apoptosis, and hydrogen peroxide H2O2, which induces apoptosis mediated by reactive oxygen species (ROS). The SAEC were continuously exposed to 0.5 µg/mL arsenic for 28 weeks, and apoptosis was examined after 24 h treatment with either Fas L or H2O2. SAEC displayed decreased cell viability and increased apoptosis after treatment with Fas L and H2O2, compared to non-arsenic treated control cells. Furthermore, treatment of these arsenic-exposed SAEC with Fas L or H2O2 induced cleavage of the DNA damage recognition protein, poly (ADP-ribose) polymerase (PARP), and the ‘effector’ caspase, Caspase-3, both canonical indicators of apoptosis. We observed increased phosphorylation of p38, a member of the MAP kinase family, following treatment with Fas L or H2O2. To confirm the involvement of p38 in the regulation of apoptosis we pretreated cells with the p38 kinase inhibitor, SB 203580 and observed a significant decrease in apoptosis. [Copyright &y& Elsevier]

We examined ultraviolet radiation (UVR)-induced DNA damage in marine micro-organisms collected from surface seawater along a latitudinal transect in the Central Pacific Ocean from 70 degrees N to 68 degrees S. Samples were collected predawn and incubated under ambient UVR in transparent incubators at in situ temperatures until late afternoon at which time they were filtered into primarily bacterioplankton and eukaryotic fractions. Cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts [(6-4)PDs] were quantified in DNA extracts using radioimmunoassays. UVB was lowest in the polar regions and highest near the equator and correlations between UVB and DNA damage were observed. The eukaryotic fraction showed significant CPDs across the entire transect; (6-4)PDs were detected only in the tropics. The bacterial fraction showed no accumulation of (6-4)PDs at any latitude, although residual (6-4)PDs were observed. Bacterial cell volumes were greatest in the sub-Arctic and northern temperate latitudes and lower in the tropics and southern hemisphere, a unique observation that parallels Bergmann's rule. A strong negative correlation was observed between cell volume and CPDs. The environmental impact of solar UVR on marine micro-organisms in the open ocean is complex and our results suggest that several factors such as DNA repair, cell size, temperature, salinity, nutrients and species composition are important in determining relative sensitivity.