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Biomedical subjects

K Hemminki

Publications and source records attributed to K Hemminki.

At least 451 records · Page 25Linked to original sources
PubMed1980

Identification of guanine-adducts of carcinogens by their fluorescence.

A fluorescence technique has been devised to identify guanosine adducts, substituted at the N7, O6 and N2 positions. The technique is based on fluorescence excitation spectra taken under neutral and alkaline conditions. At neutral pH, the N7- and O6- derivatives were fluorescent while at an alkaline pH the N7-derivatives were irreversibly destroyed with the loss of fluorescence. In alkaline solution the O6- and N2-derivatives were fluorescent but neutralization suppressed the fluorescence of the N2- derivatives. The technique was examined using methylmethanesulfonate, known to produce in the main N7- alkylation, and with diethyl sulfate known to produce N7- alkylation and to a lesser extent O6-alkylation. Fluorescence spectra typical of N 2-alkylation, in addition to N7-alkylation was produced by dimethylcarbamoylchloride.

Alkylating Agents↗
PubMed1980

Spontaneous abortions by occupation and social class in Finland.

A hospital discharge registry covering all general hospitals in Finland was used in the study of spontaneous abortions. Spontaneous abortions were analysed by the women's occupation and socio-economic class for 1973-75 inclusive. The risk of spontaneous abortion increased from social class 1 to 4 by about 50%. The occupational groups with an increased frequency of spontaneous abortions included industrial and construction work, agriculture, forestry and fishing, sales, transport and communication, services, and students and trainees. Decreased frequency of spontaneous abortions was noted among housewives, and in managerial and clerical occupations. The results suggest that socio-economic factors contribute to the rate of spontaneous abortions analogous to their known adverse effects on pre-term birth, birth weight and perinatal mortality.

Abortion, Spontaneous↗
PubMed1980

The effect of maternally inhaled styrene on embryonal and foetal development in mice and Chinese hamsters.

Pregnant mice and Chinese hamsters were exposed to styrene 6 hrs daily during the period of major organogenesis via inhalation in concentrations 250 p.p.m., and 300, 500, 750 and 1000 p.p.m., respectively. Both in mice and in Chinese hamsters embryotoxicity was raised. Some minor skeletal malformations (rib fusions, extra ribs) were noted in mice but not in Chinese hamsters.

Animals↗
PubMed1980

Covalent binding of 2-acetylaminofluorene, 2-aminofluorene, and N-hydroxy-2-acetylaminofluorene to rat liver nuclear DNA and protein in vivo and in vitro.

Binding of the hepatocarcinogen 2-acetylaminofluorene (AAF) and two metabolites, 2-aminofluorene (AF) and N-hydroxy-2-acetylaminofluorene (N-OH-AAF), to the DNA and protein of rat hepatic nuclei was examined in vitro and in a cell-free system. Three and one-half hr following a single injection of each compound in equimolar amounts. DNA contained approximately 50% more of the compounds per mg than did protein. The amount of N-OH-AAF bound to DNA was 4 times greater than that of AAF, while AF bound in intermediate amounts. When incubated with nuclei in a cell-free system, AAF seldom bound in measurable amounts, while significant amounts of N-OH-AAF and AF bound to both DNA and protein. As occurred in vivo, DNA bound more of each per mg than did protein. The amount of N-OH-AFF bound to intranuclear DNA increased 54% when an aliquot of the postmicrosomal liver fraction was added to the incubation mixture, but maximum binding of AF occurred in the absence of any other liver fraction. Thus, it was shown that two AAF metabolites, AF and N-OH-AAF, bind covalently to the DNA and protein of hepatic nuclei more readily than does AAF itself and that binding in a cell-free system parallels binding in vivo. Additional evidence suggests that rat hepatic nuclei are capable of mediating the binding of AF and N-OH-AAF to macromolecules through distinct enzyme systems. This is the first demonstration that the nucleus is capable of metabolizing AF to an electrophile that can bind covalently to DNA.

2-Acetylaminofluorene↗
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↗
PubMed1979

Effects of methylene chloride, trichloroethane, trichloroethylene, tetrachloroethylene and toluene on the development of chick embryos.

Toluene and 5 aliphatic chlorinated hydrocarbons of wide industrial use were injected into the air space of fertilized chicken eggs at 2, 3 and 6 days of incubation. The embryotoxicity was evaluated as survival and death incidences after 14 days of incubation, and also the weights and lengths of the embryos were recorded. The approximate LD50 value for trichloroethylene and trichloroethanes varied between 50 and 100 mumol/egg while for toluene, tetrachloroethylene and methylene chloride it was over 100 mumol/egg. Macroscopic malformations of various kinds were produced with doses of 5-100 mumol/egg. The teratogenic potential of the tested compounds decreased in the following order: 1,1,1-trichloroethane greater than trichloroethylene greater than methylene chloride, tetrachloroethylene, 1,1,2-trichloroethane greater than toluene greater than olive oil control.

Abnormalities, Drug-Induced↗
PubMed1979

Embryotoxicity and teratogenicity of styrene and styrene oxide on chick embryos enhanced by trichloropropylene oxide.

The effects of TCPO (trichloropropylene oxide) on the embryotoxicity and teratogenicity of styrene and styrene oxide and chick embryos were investigated. The compounds were injected into the air space of the eggs in a total volume of 25 microliter on the third day of embryogenesis. TCPO increased embryotoxicity and teratogenicity of styrene and styrene oxide. Our results present evidence that the epoxides possess embryotoxic and teratogenic properties in chick embryos.

Abnormalities, Drug-Induced↗
PubMed1979

Binding of benzo(a)pyrene into lung and thymocyte nuclear fractions.

Binding of (3H)benzo(a)pyrene into lung and thymocyte nuclear fractions is studied in short term cultures. DNA, RNA and protein in the subnuclear fractions is separated and tightly bound radioactivity is measured. Among the fractions, proteins of the matrix sediment fraction display the highest specific radioactivity. DNA has a low specific radioactivity as compared to that of RNA and protein in all fractions. In thymocyte matrix extract and chromatin fractions the specific radioactivity of RNA exceeds that of protein. Lung nonhistones display a 30 times higher specific radioactivity as compared to histones. The corresponding ratio of the thymocyte fractions is about 10.

Animals↗
PubMed1977

Protein composition of chromatin subfractions prepared from chick embryos.

Chromatins of four embryonic chick tissues were digested with DNAase II and the MgCl2-soluble and insoluble chromatin fractions were isolated. The MgCl2-soluble fractions displayed a high protein/DNA ratio and enrichment of nascent RNA as compared to the MgCl2-insoluble fractions. The recovery of DNA and protein in the MgC12-soluble chromatin of erythrocytes was much lower than that in the other cell types. The difference is likely to be associated with the low transcriptional activity of the erythrocyte chromatin. In polyacrylamide gels histones appeared to be the predominant protein constituent of the MgCl2-insoluble chromatins. Brain, skin and muscle displayed an apparently similar group of actively labelled nonhistones at 70 000 to 100 000 daltons. These nonhistones were not observed in erythrocytes. The MgCl2-soluble chromatins of erythrocytes, brain, skin and muscle had a prominent group of polypeptides at approx. 40 000 daltons. In all tissues except for erythrocytes the group of proteins was actively labelled. These polypeptides are suggested to be the major structural protein constituent of the MgCl-soluble chromatin.

Animals↗
PubMed1977

Distribution of estrogen receptors in hen oviduct chromatin fractions in the course of DNAase II digestion.

Hen oviduct chromatin was digested with DNAase II and two fractions were isolated: MgCl2-insoluble chromatin and MgCl2-soluble chromatin. The former contained 14 and 50% of the total DNA after a digestion time of 3 and 30 min, respectively. The fraction was characterized in sucrose gradients by a peak sedimenting at 11S. In the course of DNAase digestion this fraction lost most of its estrogen receptors as assayed by [3H]estradiol exchange reaction. The specific radioactivity of chromatin was particularly low in the 11S region. The MgCl2-soluble chromatin contained at most 5.1% of the total DNA. In sucrose gradients the fraction displayed peaks at 4S and 14S. After a 30 min DNAase digestion the specific radioactivity of chromatin in this fraction exceeded that of the MgCl2-insoluble fraction 7.7 fold. Material sedimenting at 14 S and at larger S values was enriched in estrogen receptors. The results suggest that estrogen receptors are unevenly distributed on hen oviduct chromain.

Animals↗