PubMed Health⌕ Search

Biomedical subjects

K Hemminki

Publications and source records attributed to K Hemminki.

At least 19 recordsLinked to original sources
PubMed1992

Molecular and genetic damage in humans from environmental pollution in Poland.

Extreme environmental pollution such as that found in the highly industrialized Silesian region of Poland has been associated with increased risk of cancer and adverse reproductive outcomes. Among the most prevalent carcinogenic and mutagenic air pollutants in Silesia are the polycyclic aromatic hydrocarbons (PAH) which are largely produced by industrial and residential combustion of coal. Molecular epidemiology aims to prevent disease by using biological markers to identify risks well before clinical onset to allow effective intervention. Here, we use a battery of biological markers to measure molecular and genetic damage in peripheral blood samples from residents of Silesia and from persons living in a rural, less polluted area of Poland. The results show that their exposure to environmental pollution is associated with significant increases in carcinogen-DNA adducts (PAH-DNA and aromatic adducts), in sister chromatid exchange including high-frequency cells, and in chromosomal aberrations as well as a doubling in the frequency of ras oncogene overexpression. We found that aromatic adducts on DNA were significantly correlated with chromosomal mutation, providing us with a molecular link between environmental exposure and a genetic alteration relevant to cancer and reproductive risk.

Adult↗
PubMed1992

Magnetic fields of video display terminals and spontaneous abortion.

The aim of this study was to examine whether work with a video display terminal and exposure to the magnetic fields of video display terminals are related to spontaneous abortion. The study was conducted among women employed as bank clerks and clerical workers in three companies in Finland. The cases (191 spontaneous abortions) and controls (394 births) were identified from Finnish medical registers for the years 1975-1985. Use of video display terminals was defined using the workers' own reports and information provided by the companies. The assessment of exposure to the magnetic fields was based on measurements of the fields of video display terminals. The odds ratio for spontaneous abortion for working with video display terminals was not increased (odds ratio = 1.1, 95% confidence interval 0.7-1.6). However, the odds ratio for workers who had used a video display terminal with a high level of extremely low frequency magnetic fields (> 0.9 microT) was 3.4 (95% confidence interval 1.4-8.6) compared with workers using a terminal with a low level of these magnetic fields (< 0.4 microT). Adjustment for ergonomic factors and mental work load factors changed the odds ratio for magnetic field exposure only very slightly. The findings suggest the need for future studies with assessment of exposure to the magnetic fields in the actual working environment to confirm the possible risk.

Abortion, Spontaneous↗
PubMed1992

Serum oncoproteins and growth factors in asbestosis and silicosis patients.

Levels of 9 different oncoproteins and growth factors were assayed by immunoblotting with monoclonal antibodies in 91 serum samples collected between March 1983 and August 1987 from 46 pneumoconiosis patients (36 asbestosis, 10 silicosis) at high risk for the development of cancer. Follow-up of these patients through June 1991 showed that 18 had developed cancer (11 lung, 2 pleural mesothelioma, 2 transitional-cell carcinomas of the urinary bladder, 1 osteosarcoma, 1 non-Hodgkin's lymphoma, 1 adenocarcinoma of the gallbladder). Increased serum levels of ras oncogene-related protein (p21) were found in 7 of the 18 patients who developed cancer (5 lung, 2 pleural mesothelioma) versus 2 of the 28 patients without cancer, a statistically significant difference (p = 0.012). In addition, 6 of the 7 p21-positive cancer cases had positive serum samples prior to clinical diagnosis of disease (average = 16.3 months, range = 3-26 months prior to diagnosis), suggesting that elevated serum p21 levels may be a useful marker for earlier detection in a significant percentage of respiratory malignancies. Finally, elevated serum levels of PDGF-related protein were detected significantly more frequently in advanced pneumoconiosis cases (ILO radiographic classification of 2/1 or greater) than in less advanced cases (80% vs. 41.9%; p = 0.016), and there was a tendency for these PDGF-positive patients to have progression of their disease (68.2% vs. 41.7%; p = 0.065), suggesting that elevated serum PDGF levels may be a marker for the development of severe and progressive pneumoconioses.

Aged↗
PubMed1992

Use of chemical, biochemical, and genetic markers in cancer epidemiology and risk assessment.

New molecular methods have been developed to be used in assessing exposure to and effects of genotoxic and carcinogenic compounds. DNA and protein adducts are measures or surrogates of target dose. Molecular methods are available to probe mutations in oncogenes, antioncogenes, and other specific genes. Furthermore, concentrations of oncoproteins can be determined in biological fluids. If a close link is established between these markers and risk of cancer, they can be used as independent endpoints in the prevention of cancer.

Biomarkers↗
PubMed1992

7-Methylguanine levels in DNA of smokers' and non-smokers' total white blood cells, granulocytes and lymphocytes.

The effect of smoking was investigated on the formation of 7-methylguanines in human peripheral white blood cells. DNA was isolated from total white blood cells, granulocytes and lymphocytes from 10 smokers and 10 non-smokers. 32P-Postlabeling was performed by using anion-exchange chromatography enrichment of adducts. In smokers the mean DNA adduct levels were 6.9, 4.7 and 23.6 7-methylguanine residues/10(7) nucleotides in total white blood cells, granulocytes and lymphocytes respectively. The corresponding values in non-smokers were 3.4, 2.8 and 13.5 adducts/10(7) nucleotides. The mean adduct level was significantly higher in lymphocytes than in total white blood cells or granulocytes both in smokers and in non-smokers. The mean adduct levels differed significantly between smokers and non-smokers.

Adult↗
PubMed1992

Some quantitative considerations about DNA adduct enrichment procedures for 32P-postlabelling.

The concentrations of 2'-deoxyribonucleoside-3'-monophosphates remaining in calf-thymus DNA digests after nuclease P1 digestion or extraction into 1-butanol, the most commonly used adduct enrichment procedures prior to the application of the 32P-postlabelling assay, were measured using HPLC and 32P-postlabelling methods. When 10 micrograms of DNA digested to mononucleotides was used, the total amount of nucleotides remaining in the samples were approximately 4 and approximately 14 pmol after nuclease P1 treatment or 1-butanol extraction respectively. The influence of various concentrations of normal nucleotides on the labelling efficiency of a 2'-deoxyguanosine-3'-monophosphate adduct of benzo[a]pyrene diol-epoxide was also studied and found to depend upon the ratio of normal nucleotides/adducted nucleotides present in the sample. Also, the ATP/normal nucleotides ratio in the phosphorylation reaction may affect the quantitation of the adducts and thus deserves due consideration.

1-Butanol↗
PubMed1992

Determination of malonaldehyde-modified 2'-deoxyguanosine-3'-monophosphate and DNA by 32P-postlabelling.

The 32P-postlabelling assay was used to determine adducts arising upon the reaction of malonaldehyde with 2'-deoxyguanosine-3'-monophosphate. The adducts formed were isolated, structurally characterized and identified as 3-(2-deoxy-beta-D-erythro-pentafuranosyl)pyrimido[1,2-alpha] purin-10(3H)-one. The kinetics of phosphorylation by T4 polynucleotide kinase was studied using 500 fmol of the synthesized standard and found to reach its maximum after 1 h of incubation. A 60% labelling efficiency was obtained at low concentrations of substrate. The adducted substrate was detected at the sub-femtomolar level. Sensitivity of the adducts towards nuclease P1 3'-dephosphorylation was also tested. The same adduct could be detected from calf thymus DNA that had been reacted in vitro with malonaldehyde, and in DNA isolated from mice treated with [14C]malonaldehyde. DNA adducts formed in vitro were isolated after enzymatic digestion to mononucleotides followed by HPLC fractionation or nuclease P1 digestion of normal nucleotides. A combination of the two procedures proved to be the method of choice for the isolation of the malonaldehyde-DNA adducts formed in vivo prior to applying the 32P-postlabelling assay.

Animals↗
PubMed1992

Paternal occupational lead exposure and congenital malformations.

STUDY OBJECTIVE: The aim was to investigate whether occupational exposure to lead in fathers is associated with congenital malformation in their children. DESIGN: The study was a retrospective case-control study, nested within the wives of men biologically monitored for inorganic lead. Information on pregnancy outcome was obtained from medical registers. SUBJECTS: Cases were defined as wives with malformed child during 1973-82. Three age matched controls were selected for each case from the wives who had given birth during 1973-1983. The final study population was 27 cases and 57 controls. MEASUREMENTS AND MAIN RESULTS: Paternal lead exposure was assessed with blood lead measurements and data obtained from a questionnaire. The response rate was 67% among the cases and 76% among the controls. The odds ratio (OR) of congenital malformation for paternal lead exposure was increased (OR 2.4, 95% confidence interval 0.9-6.5), although not reaching statistical significance. The odds ratios varied from 1.9 to 3.2, when adjusted for one potential confounding variable at a time. CONCLUSIONS: Because of the small numbers and low participation, this study offers limited support for the hypothesis that paternal lead exposure is associated with congenital malformation. Further epidemiological studies on the reproductive hazards of paternal lead exposure are needed.

Abnormalities, Drug-Induced↗
PubMed1992

Analysis of deoxyribonucleic acid adducts in workers.

Repeated blood samples were obtained from volunteers who were occupationally exposed to polycyclic aromatic hydrocarbons in a Finnish iron foundry. Aromatic adducts were determined in white blood cell deoxyribonucleic acid of the subjects with the 32P-postlabeling technique after nuclease P1 treatment and butanol extraction, which showed no major difference. When repeated samples were analyzed, it appeared that the oldest ones displayed the lowest adduct levels, probably due to the instability of the adducts upon storage at -20 degrees C. The workers tended to maintain their adducts at a uniform level, a finding suggesting the contribution of host factors in the control of adduct levels.

DNA↗
PubMed1992

Use of molecular biology techniques in cancer epidemiology.

Biochemical techniques have been applied for years in clinical medicine to unravel disease indicators and mechanisms. The study design, resembling that of a case-referent study, has been to compare diseased and healthy individuals. Conclusive results have been obtained for diseases in which relatively few factors cause high risks. The same study design has been maintained with sophisticated methods of molecular biology, which have revealed many types of deoxyribonucleic acid lesions associated with cancer. It is likely that the relatively simple cross-sectional and case-referent studies require input from epidemiologists to unravel multifactorial etiologies. Longitudinal approaches may be the only alternative with which to evaluate the role and usefulness of the application of molecular biology markers in studies of cancer.

DNA Mutational Analysis↗
PubMed1991

Quantitation of the 32P-postlabeling reaction using cyclic N1,N2 and C8 modified deoxyguanosine 3'-monophosphates as substrates.

The 32P-postlabeling technique was used to investigate the efficiency of phosphorylation reaction by T4 polynucleotide kinase using seven synthetic adducted deoxyguanosine 3'-monophosphates. The adducts included cyclic N1,N2 derivatives and the C8 adduct of 4-aminobiphenyl. The adducted substrates were detected at a subfemtomole sensitivity except for one of the diastereomeric propanoguanine derivatives. In general, the recommended conditions were found to be proper for an efficient phosphorylation of the adducts studied. Sensitivity of the adducts to the 3'-dephosphorylation reaction of nuclease P1 was also tested. All the complex cyclic adducts were resistant towards P1. However, the ethenoguanine and 4-aminobiphenyl adducts were relatively sensitive towards P1. No differences were noted between diastereomers.

Chromatography, Thin Layer↗
PubMed1991

DNA adducts and other biological markers in risk assessment for environmental carcinogens.

In order to validate a number of biologic markers as indicators of effective dose or potential risk, we have applied them in related cross-sectional, longitudinal and case-control studies. Biologic markers such as carcinogen-DNA adducts and activated oncogenes have already provided insights into mechanisms of chemical carcinogenesis. They have also given information regarding the extent of interindividual variation in biologic response within the human population. These results are directly relevant to quantitative risk assessment. However, more research is needed to establish quantitative links between biologic markers and human risk of cancer.

Biomarkers↗
PubMed1979

Histone gene switch in the sea urchin embryo. Identification of late embryonic histone messenger ribonucleic acids and the control of their synthesis.

During embryogenesis in the sea urchin Strongylocentrotus purpuratus, there is a shift from one histone mRNA population to another. The early and late embryonic histone mRNAs, previously shown to differ considerably in sequence from each other by hybrid melting studies, are shown here to differ also in electrophoretic mobility on polyacrylamide gels as the positions of the early and late mRNAs are completely noncoincident. The various species of both early and late samples are identified as particular histone mRNAs by hybridization to cloned histone DNAs containing part of the early-type repeat unit or to restriction enzyme fragments derived from these unit. Four bands in the early mRNA sample are identified as H1, H3, H2A " H2B, and H4 mRNA while at least 10 bands can be seen in the late mRNA preparation with unambiguous identification of H1, H2B, and H4 mRNAs. A cluster of late species is shown to contain both H3 and H2A mRNA. When a polysomal RNA preparation from the 26-h embryo is hybridized to the histone DNA, eluted, and then translated in vitro in a wheat germ system, the histone products migrate in the position of late histones when subjected to electrophoresis on Triton X-urea gels. Using DNA which contains genes for H2A + H3 or H2A alone, we demonstrate the specificity of the early-type DNA probes for these two late histones. Therefore, by hybridization of newly synthesized RNAs and translation of the total polysomal RNA present in the late embryo, it is shown that mRNAs for all five histone classes may cross-react with the cloned early-type DNA. The hybrids formed, however, are much less stable than those formed with the early histone mRNA. In vitro translation of total cytoplasmic RNA from various embryonic stages indicates that transition between the two classes occurs during most of the blastula period.

Animals↗
PubMed1979

Fluorescence study of DNA alkylation by epoxides.

A simple fluorescence assay was devised to measure alkylation of guanine. The assay was tested with simple epoxides: propylene oxide, glycidol, epichlorohydrin, trichloropropylene oxide and styrene oxide, which are known to vary considerably in their mutagenic potency. The order of reactivity parallelled the mutagenic potency, trichloropropylene oxide being the most reactive alkylating agent. Each epoxide alkylated deoxyguanosine faster than single-stranded DNA, at equal concentrations of guanine. Single-stranded DNA was alkylated substantially faster than was double-stranded DNA. The reaction products with each substrate were analysed by thin-layer chromatography and exhibited similar Rf-values. It was concluded that polymers, particularly double-stranded DNA, reacted slower than deoxyguanosine due to the properties of polymers in solution rather than the unavailability of reactive sites for alkylation.

1-Propanol↗