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Biomedical subjects

K Hemminki

Publications and source records attributed to K Hemminki.

At least 433 records · Page 24Linked to original sources
PubMed1981

Reactions of beta-propiolactone, beta-butyrolactone and gamma-butyrolactone with nucleic acids.

Reactivity of beta-propiolactone, beta-butyrolactone and gamma-butyrolactone with guanosine, RNA, DNA and 4-(p-nitrobenzyl)pyridine was studied. beta-Propiolactone was 50--100 times more reactive with all the nucleophiles than beta-butyrolactone whereas gamma-butyrolactone was completely inactive. The rate of alkylation by the lactones was guanosine greater than RNA = denatured DNA greater than double-stranded DNA. The type of the adducts formed were characterized by fluorescence and ultraviolet spectroscopy. Similar alkylation products were formed by the two lactones. The main sites alkylated were N-1 at adenosine, N-3 at cytidine and N-7 at guanosine. The results suggest that the carcinogenic potency of the lactones correlates with their reactivity rather than with specificity of the adducts formed.

4-Butyrolactone↗
PubMed1981

Metabolism and genotoxicity of styrene.

An overview on the metabolism and genotoxicity of styrene is given in this article. The mutagenic potency of styrene has been confirmed in a number of test systems providing the metabolic activation of styrene. Styrene is converted to styrene-7,8-oxide as catalyzed by cytochrome P-450 cored enzyme complex. Styrene-7,8-oxide is mutagenic in prokaryotic and eukaryotic test systems without metabolic activation. It reacts with nucleic acid bases, especially with deoxyguanosine producing 7-alkylguanine and deoxycytidine producing N-3 alkylcytosine. Quite recently, styrene-7,8-oxide has been found to be a potent carcinogen in rats. In human whole blood cultures, styrene is metabolized into styrene-7,8-oxide. Styrene is able to induce both SCEs and chromosomal aberrations in cultured lymphocytes. The clastogenic action of styrene can be explained by the metabolism of styrene into styrene-7,8-oxide in cultured human blood cells. Although also an arene oxide, styrene-3,4-oxide, has been suggested in the biotransformation of styrene, the evidence so far supports the view that the vinyl group oxidation and oxirane formation plays a predominant role in the genotoxicity of styrene.

Animals↗
PubMed1981

Alkylation of guanosine and 4-(p-nitrobenzyl)-pyridine by styrene oxide analogues in vitro.

In vitro alkylation activity of styrene oxide (SO) and three of its analogues, 4-vinyltoluene oxide (VTO), 3,5-dimethylstyrene oxide (DMSO), and 4-nitrostyrene oxide (NSO) was assayed using 4-(p-nitrobenzyl)pyridine (NBP) and guanosine as nucleophiles. Hydrolysis rates were also determined. The half-lives of VTO, DMSO, SO, and NSO were 8, 11, 40, and 60 h, respectively in aqueous solution. The rate of NBP alkylation correlated with the rate of hydrolysis. By contrast, the rates of guanosine alkylation were quite different: SO greater than VTO greater than DMSO. NSO did not react with guanosine. Fluorescence an ultraviolet spectroscopic data on the guanosine adducts indicated that SO, VTO, and DMSO formed main alkyl products at N-7.

Alkylation↗
PubMed1981

Reactions of formaldehyde with guanosine.

Formaldehyde reacted with guanosine and the products were assayed using fluorescence spectroscopy at different pHs. The reaction products were fluorescent in alkali only as was found with commercial N-2 methylguanosine. Thus, formaldehyde appeared to react with N-2 of guanosine. The reaction was completed with 30s both at 0 degrees C or at 21 degrees C. The stability of the reaction products was further investigated by the addition of glycine. When formaldehyde was allowed to react with guanosine for 30s, 90% of the fluorescence disappeared when glycine was added suggesting a labile adduct such as a methylol derivative. By contrast, after a 20 h incubation only 20% of fluorescence was abolished with glycine suggesting a stable adduct such as a methylene derivative.

Chemical Phenomena↗
PubMed1981

Childhood cancer and parental occupation in Finland.

A case-control study was conducted of the occupations of parents of children under 15 with diagnosed malignancies. The total series contained all childhood cancers cases reported to the Finnish Cancer Registry during the period 1959-75. The parental occupations, recorded at the time of pregnancy, were collected from maternity welfare centres. The cases were analysed as a singly group or as subgroups according to the diagnoses-brain tumours, leukaemia, and all other malignancies. The maternal occupations found more frequently among cases than controls included farmers' wives (1959-68 only), pharmacists, saleswomen, bakers, and factory work of an vehicle driving, machine repair, painting, and the work of men who gave an academic degree as their occupation. Some of these occupations involve possible exposure to harmful chemicals, although chance correlations cannot be excluded.

Adolescent↗
PubMed1981

Congenital malformations and maternal occupation in Finland: multivariate analysis.

The Finnish Register of Congenital Malformations was used in a multivariate analysis to explore the associations between maternal occupation in industry and children born with central nervous system (CNS) or musculoskeletal or oral cleft malformations. Possible confounding factors were selected in preliminary screening of risk indicators for malformations. These factors included characteristics of the mother, the child, and the family; maternal illnesses; an maternal medication at the time of pregnancy. Tobacco smoking was a confounding factor for all type of malformations; number of children born to the mother, maternal age, malformations in the family, number of rooms occupied by the family, sex of the child, threatened abortion, and continuous medication of the mother during the first trimester confounded the association for certain type of malformations. After adjusting for confounding factors, maternal occupation in industrial trades significantly correlated with CNS, oral cleft, and musculoskeletal malformation in the offspring. Maternal occupation in industry and construction only was significantly associated with CNS malformations in the offspring but the associations with oral cleft and musculoskeletal malformations were not significant.

Adult↗
PubMed1980

Comparison of alkylation rates and mutagenicity of directly acting industrial and laboratory chemicals: epoxides, glycidyl ethers, methylating and ethylating agents, halogenated hydrocarbons, hydrazine derivatives, aldehydes, thiuram and dithiocarbamate derivatives.

Groups of industrial and laboratory chemicals were tested for their alkylation activity using 4-(p-nitrobenzyl)-pyridine and deoxyguanosine as nucleophiles. The alkylation activity was compared with mutagenicity of the chemicals to E. coli WP2 uvrA without metabolic activation. All the epoxide-containing compounds including simple epoxides and glycidyl ethers elicited alkylation activity and mutagenicity. Furthermore there was a reasonable correlation between the rate of alkylation and the mutagenic potency. All the methylating and ethylating compounds tested were active but no correlation was observed between the rate of alkylation and the mutagenic potency, apparently due to the different types of alkylation products formed. The other compounds tested including halogenated hydrocarbons, hydrazine derivatives, aldehydes, thiuram and dithiocarbamate derivatives elicited a slow or no alkylation activity while many of the compounds were mutagenic. There was no evidence among the chemicals tested of an alkylating non-mutagen. Thus evidence of alkylation activity appears to indicate mutagenic risk.

Aldehydes↗
PubMed1980

Spontaneous abortions among women employed in the metal industry in Finland.

Spontaneous abortions were analyzed among Finnish metal workers between 1973 and 1976. The information on the workers (35,000 women) was obtained from the files of the Union of Metal Workers; information on the abortions was obtained from the Hospital discharge registry of the National Board of Health. Among metal workers 195 spontaneous abortions were recorded. The proportion of spontaneous abortions was 7.82% (spontaneous abortions/pregnancies, rate) and 13.79% (spontaneous abortions/births, ratio) of which the latter figure was significantly higher (P < 0.05) than the respective one among all Finnish women. Both the rate and the ratio were significantly increased upon joining the Union as analyzed from an age-standardized material. A particular risk industry appeared to be the production of radios, televisions, and their components. An exposure to solder fumes was suggested to explain the increased risk.

Abortion, Spontaneous↗
PubMed1980

Occupational chemicals tested for teratogenicity.

Literature was surveyed concerning the teratological testing of chemicals, to which large numbers of workers are occupationally exposed. They include metals, plastics monomers and additives, solvents, and other organic chemicals. The effective doses used in the studies were compared to the potential exposures in the occupational environment as regulated by hygienic standards. In light of the animal experiments, the TLVs for some organic chemicals, particularly for acrylonitrile, methacrylate esters, styrene, carbon disulfide, chloroform, methylene chloride, toluene and xylene, appeared too high to provide absolute safety for pregnant workers. The mechanisms of teratogenesis and the validity of the animal experiments were also considered.

Animals↗
PubMed1980

Alkylation products of DNA bases by simple epoxides.

The reaction products of a series of epoxides with deoxyribonucleosides were characterized using ultraviolet, and NMR spectroscopy. The epoxides included structural analogues which are known to differ extensively in their mutagenic potency: propylene oxide, glycidol, epichlorohydrin, trichloropropylene oxide and styrene oxide. Trichloropropylene oxide, epichlorohydrin and glycidol reacted with deoxyguanosine producing a major adduct of 1,7-(or 1,9-)dialkylguanine. All of the epoxides produced a 7-alkylguanine adduct, with the possible exception of styrene oxide. Propylene oxide, glycidol and epichlorohydrin reacted with deoxyadenosine at N-6. Glycidol, trichloropropylene oxide and styrene oxide reacted with deoxycytidine at N-3. It was concluded that the structurally related epoxides tend to react largely in a uniform way with nucleic acid bases. Thus, the reaction rates rather than the major adducts explain the differential mutagenicity of the epoxides.

Alkylation↗
PubMed1980

Alkylation of rat serum proteins by dimethylnitrosamine and acetylaminofluorene.

The labelling of rat serum proteins was studied after i.p. injections of radioactive dimethylnitrosamine (DMN) or acetylaminofluorene (AAF). Protein-bound radioactivity decayed with an apparent half-life of 49 h and 35 h after DMN and AAF treatment, respectively. Methylated amino acid residues were indentified from DMN-treated animals using thin-layer chromatography of the serum protein hydrolysates. The main methylation products were shown to be S-methylcysteine and 1-methylhistidine. The possibilities of monitoring carcinogen and mutagen exposure by analysing the alkylation of serum proteins are discussed.

2-Acetylaminofluorene↗