Impact of Radiation Biology on Fundamental in Biology

Research supported by OHER and its predecessors has as one of its major goals an understanding of the effects of radiation at low doses and dose rates on biological systems, so as to predict their effects on humans. It is not possible to measure such effects directly. They must be predicted from basic knowledge on how radiation affects cellular components such as DNA and membranes and how cells react to such changes. What is the probability of radiation producing human mutations and what are the probabilities of radiation producing cancer? The end results of such studies are radiation exposure standards for workers and for the general population. An extension of these goals is setting standards for exposure to chemicals involved in various energy technologies. This latter problem is much more difficult because chemical dosimetry is is a primitive state compared to radiation dosimetry

Transcriptional analysis of temporal gene expression in germinating Clostridium difficile 630 endospores.

Clostridium difficile is the leading cause of hospital acquired diarrhoea in industrialised countries. Under conditions that are not favourable for growth, the pathogen produces metabolically dormant endospores via asymmetric cell division. These are extremely resistant to both chemical and physical stress and provide the mechanism by which C. difficile can evade the potentially fatal consequences of exposure to heat, oxygen, alcohol, and certain disinfectants. Spores are the primary infective agent and must germinate to allow for vegetative cell growth and toxin production. While spore germination in Bacillus is well understood, little is known about C. difficile germination and outgrowth. Here we use genome-wide transcriptional analysis to elucidate the temporal gene expression patterns in C. difficile 630 endospore germination. We have optimized methods for large scale production and purification of spores. The germination characteristics of purified spores have been characterized and RNA extraction protocols have been optimized. Gene expression was highly dynamic during germination and outgrowth, and was found to involve a large number of genes. Using this genome-wide, microarray approach we have identified 511 genes that are significantly up- or down-regulated during C. difficile germination (p≤0.01). A number of functional groups of genes appeared to be co-regulated. These included transport, protein synthesis and secretion, motility and chemotaxis as well as cell wall biogenesis. These data give insight into how C. difficile re-establishes its metabolism, re-builds the basic structures of the vegetative cell and resumes growth

Associations of Cumulative Sun Exposure and Phenotypic Characteristics with Histologic Solar Elastosis

Solar elastosis adjacent to melanomas in histologic sections is regarded as an indicator of sun exposure although the associations of ultraviolet (UV) exposure and phenotype with solar elastosis are yet to be fully explored

Genome Instability and Bleomicin Sensitivity Test

Procjena individualne osjetljivosti na mutagene često je dio istraživanja u epidemiološkim studijama koje prate pojavnost zloćudnih bolesti u populacijama. Posljedica djelovanja mutagena u genomu izloženih osoba jest nastanak određene, manje ili veće, količine oštećenja, uvjetovane individualnim razlikama u osjetljivosti. Viša razina takve genomske nestabilnosti znači opasnost (rizik) od razvoja zloćudnih bolesti. Interindividualne razlike u odgovoru na mutagene obično se povezuju i s promijenjenom (većinom smanjenom) sposobnosti (kapacitetom) za popravak DNA. Citogenetičke studije su pokazale da je genom tumorskih stanica nestabilniji od normalnih, a time i skloniji akumuliranju oštećenja, bilo da je nestabilnost uzrokovana nasljeđem, izloženošću ili kombinacijom tih dvaju učinaka. U oboljelih ispitanika utvrđena je povećana učestalost kromatidnih i kromosomskih aberacija naspram normalne populacije te sklonost razvoju određenih vrsta neoplazija. U praćenju povezanosti promijenjenog odgovora i pojavnosti tumora služe nam različiti biomarkeri. Kao indirektni pokazatelji uspješnosti popravka DNA često se rabe testovi osjetljivosti na mutagene u kulturama limfocita periferne krvi. Jedan od takvih testova je i bleomicinski test. Radiomimetik i citostatik, a po strukturi glikopeptid, bleomicin se u stanici prevodi u aktivni oblik sposoban cijepati molekulu DNA što uzrokuje brojne jednolančane i dvolančane lomove. Kao jednostavna i jeftina metoda, zasniva se na utvrđivanju ukupnog broja jednolančanih lomova u kromosomima limfocita uzgajanih u staničnoj kulturi koji su u uvjetima in vitro tijekom kasne G2-faze staničnog ciklusa bili izloženi bleomicinu. Ovaj revijalni rad daje pregled utjecaja raznih faktora na rezultate samog testa i pokazuje njegovu široku primjenu u proučavanju genomske nestabilnosti koju najčešće uzrokuje kombinacija raznih faktora.Estimation of individual susceptibility to mutagens is often a part of epidemiological studies monitoring the appearance of malignant disease in different populations. Genome exposure to mutagens can lead to DNA damage. The rate of damage depends on individual differences in response, which are usually associated with differences in DNA repair capacity. Cytogenetic studies have shown that the genome of tumour cells is less stable than normal cells and therefore accumulates more damage. Tumour patients show a higher frequency of chromatid and chromosomal aberrations and a predisposition to certain types of tumours. One of the common biomarkers used in monitoring tumour appearance and changed response to DNA damage is the bleomycin test. In its active form, bleomycin (glycopeptid) is a radiomimetic cytostatic that can damage the DNA molecule and cause multiple single and double strands. The bleomycin test is simple and inexpensive, and is based on scoring chromatid breaks in lymphocytes in vitro exposed to bleomycin during the late G2 phase of the cell cycle. This review looks into different factors that may affect test results and discusses its wide implementation in studies of genome instability usually caused by a combination of factors

The Ultraviolet Light Inactivation of ΦX174 Bacteriophage at Different wave Lengths and pH's

The bacterial virus, ΦX174, which contains a single strand of DNA has been inactivated by different wave lengths of monochromatic ultraviolet light at pH 7, 2, and 12. The action spectra for inactivation at these three pH's all showed minima at 2400 A rather than at 2300 A, which is the characteristic absorption minimum of DNA. The shapes of the action spectra have been analyzed in terms of the effects of absorbed light on the pyrimidines and purines rather than the effect on nucleoprotein. In this interpretation the pyrimidines are at least 2 to 3 times more sensitive than the purines. The quantum yield for inactivation of the virus at 2650 A and pH 7 is 0.006. The quantum efficiency for quanta absorbed in the pyrimidines is 0.0085 and for the purines 0.0035. It is pointed out that action spectra for single- and double-stranded polynucleotides should have minima at different wave lengths, and that this difference may be used to distinguish between these two configurations in vivo

The hazards of space travel

Before sending out astronauts on an interplanetary mission, we need to investigate how the conditions in space affect human health. The International Space Station is therefore of huge importance to ensure the health of a spaceship crew travelling to other planet

Impact of Radiation Biology on Fundamental in Biology

Research supported by OHER and its predecessors has as one of its major goals an understanding of the effects of radiation at low doses and dose rates on biological systems, so as to predict their effects on humans. It is not possible to measure such effects directly. They must be predicted from basic knowledge on how radiation affects cellular components such as DNA and membranes and how cells react to such changes. What is the probability of radiation producing human mutations and what are the probabilities of radiation producing cancer? The end results of such studies are radiation exposure standards for workers and for the general population. An extension of these goals is setting standards for exposure to chemicals involved in various energy technologies. This latter problem is much more difficult because chemical dosimetry is is a primitive state compared to radiation dosimetry