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Biomedical subjects

K Hemminki

Publications and source records attributed to K Hemminki.

At least 397 records · Page 22Linked to original sources
PubMed1984

Human exposure to potentially carcinogenic compounds.

Average exposures to suspected carcinogens were surveyed for the population in Finland. Alcohol, food and tobacco constitute the largest sources of exposure. Occupational populations may be more exposed than the population at large, by many orders of magnitude. For example, occupational exposure to airborne asbestos and trichloroethylene may be 10 000 times higher than exposure outside workplaces. Application of exposure data to health surveillance and epidemiological research is discussed.

Air Pollutants↗
PubMed1983

Smoking and the occurrence of congenital malformations and spontaneous abortions: multivariate analysis.

A multivariate analysis was carried out with retrospective data on the effects of tobacco smoking on congenital malformations and spontaneous abortions. Congenital malformations were collected from the Finnish Register of Congenital Malformation. Tens of possible confounding variables, including maternal and family characteristics, obstetric history, medicine taking, and diseases during the pregnancy, were taken into consideration. In the final analysis 13 confounders were controlled. The odds ratios for the smoker's child to be born with central nervous system, oral cleft, or musculoskeletal malformations were 1.25, 1.25, and 0.75, respectively. All the differences were statistically nonsignificant. The effect of smoking on spontaneous abortions was analyzed by means of a questionnaire study on hospital personnel. The smokers of over 10 cigarettes per day had more spontaneous abortions than the nonsmokers, but the differences were not significantly statistically. The data were controlled for age, parity, and coffee and alcohol drinking.

Abortion, Spontaneous↗
PubMed1983

Embryotoxicity of industrial chemicals on the chicken embryo: dithiocarbamates.

Seven dithiocarbamates and three acetates were tested for teratogenicity and lethality in three-day chicken embryos. These included: cadmium diethyldithiocarbamate (CdDE), zinc diethyldithiocarbamate (ZnDE), zinc ethylphenyldithiocarbamate (ZnEP), zinc dibutyldithiocarbamate (ZnDB), copper dimethyldithiocarbamate (CuDM), tellurium diethyldithiocarbamate (TeDE), and piperidine pentamethylenedithiocarbamate (PPM), cadmium acetate (CdAC), copper-(II)acetate (CuAC), and zinc acetate (ZnAC). The parameters measured were early deaths, recorded within two days of injection, late deaths of malformed embryos, late deaths of nonmalformed embryos, and malformed survivors. The order of embryotoxicity decreased as follows: CdAC greater than CdDE greater than ZnDE greater than or equal to ZnEP greater than or equal to ZnDB greater than CuDM greater than TeDE greater than CuAC greater than PPM greater than ZnAC. The only exception to this order was the relatively weak teratogenicity of the metal acetates as compared to dithiocarbamates. Cadmium and zinc dithiocarbamates were potent embryotoxic agents eliciting lethality and malformations at doses of 1 to 10 nmole per egg. Most embryonic deaths occurred at stages 29 to 31, and most of the dead embryos were malformed.

Acetates↗
PubMed1983

Embryotoxicity of sixteen industrial amines to the chicken embryo.

Sixteen amine compounds that are used in the rubber industry, and sodium nitrite, were tested on three-day chicken embryos for embryotoxicity. The parameters measured were: early deaths recorded within two days of injection, late deaths of malformed embryos, late deaths of non-malformed embryos and malformed survivors. The most embryotoxic chemicals were N-phenyl-N'-isopropyl-p-phenylenediamine, N,N,N-triethylethylenediamine, N,N'-dicyclohexyl-p-phenyleneamine and triethylamine, with total effect ED50 values, including deaths and malformations, between 0.11 and 0.90 mumol per egg. The ED50 values for triethylenetetramine, N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine, triethanolamine, N-phenyl-2-naphtylamine, aniline and N-nitrosodiphenylamine ranged from 1.1 to 7.0 mumol per egg. Sodium nitrite was the least potent, with an ED50 of 22 mumol per egg. Six chemicals produced no effects. They probably did not reach the embryo. The four most potent chemicals, together with aniline, caused the highest frequencies of malformations.

Amines↗
PubMed1983

Reactivity, SCE induction and mutagenicity of benzyl chloride derivatives.

Benzyl chloride, benzyl bromide, p-methylbenzyl chloride, and p-nitrobenzyl chloride were used to study chemical reactivity with 4-(p-nitrobenzyl)-pyridine (NBP), and with guanosine in vitro, in relation to mutagenic potency in S. typhimurium and sister chromatid exchange (SCE) induction in CHO cells. Benzyl bromide was found to be the most reactive compound, followed by p-methylbenzyl chloride, benzyl chloride and p-nitrobenzyl chloride. The order of mutagenicity was p-nitrobenzyl chloride much greater than benzyl bromide greater than benzyl chloride approximately equal to p-methylbenzyl chloride. The compounds tested caused base-pair mutations only. The order of SCE-inducing ability decreased as follows: benzyl bromide greater than benzyl chloride approximately equal to p-nitrobenzyl chloride approximately equal to p-methylbenzyl chloride. The particularly high mutagenicity of p-nitrobenzyl chloride in bacteria may be due to reactions other than direct aralkylation, or it may react particularly actively with DNA. Among the other compounds, benzyl bromide was the most active aralkylating compound, mutagen and SCE inducer. The results suggested that reaction of N2 of guanine, as compared with N-7 of guanine, failed to show any remarkable mutagenicity or SCE induction, since p-methylbenzyl chloride, reacting preferentially at N2 of guanosine, failed to show unexceptional potency.

Animals↗
PubMed1983

Urinary excretion products after the administration of 14C-acetaldehyde to rats.

Rats were injected with 120 micro Ci of 14C-acetaldehyde containing carrier acetaldehyde, and the urinary excretion products were assayed by cation exchange chromatography, resolving five main peaks of radioactivity. Urine contained 6% of the dose of 14C-acetaldehyde administered. The main urinary product of acetaldehyde, fraction 5, was produced via acetate. Acetate was also identified in the urine. Two cysteine adducts, probably isomeric metabolites of 2-methylthiazolidine-4-carboxylic acid, were detected. They constituted about 2% of the radioactivity in the urine collected 48 h after the administration of 14C-acetaldehyde. They appeared to retain a carboxylic group. When the reaction mixture of 14C-cysteine and acetaldehyde was injected into a rat, the half-lives of the two tiazolidine derivatives was 10 h. Only 13.6% of the radioactivity was detected in the urine suggesting ready metabolism of 2-methylthiazolidine-4-carboxylic acid.

Acetaldehyde↗
PubMed1983

Timing and rates of synthesis of early histone mRNA in the embryo of Strongylocentrotus purpuratus.

The level of early histone mRNA in Strongylocentrotus purpuratus changes abruptly at 6 hr of development, increasing an average of 10-fold by 9-10.5 hr and then decreasing over 2-fold by 13.5-15 hr. These changes occur when the late embryonic mRNA is still a very minor component of histone gene transcription. The exact values of increase and decrease of mRNA level vary from experiment to experiment and may reflect the conditions of embryos at different times. The instantaneous rate of synthesis of histone RNA per embryo increases from at least 47 fg/min at 6 hr to 114 fg/min at 9 hr and then drops to 29 fg/min at 12 hr. The rate of mRNA accumulation is lower: 20, 43, and 12 fg/min, respectively. On a per cell basis, however, the rate of synthesis and accumulation is highest at 6 hr and continuously decreases to 1/20 the level per cell at 12 hr. The transcriptional rates and relative mRNA increases taken together predict an average increase from 0.16 to 0.24 pg/embryo (6-10 X 10(5) molecules) per mRNA species in the egg to 1.6 to 2.4 pg/embryo (6-10 X 10(6) molecules) at 10.5 hr. The transcription rates indicate that at the maximal values we obtained, about two to three molecules of each histone RNA are made per gene copy per minute. The half-life of the histone mRNAs in the period from 6 to 13.5 hr probably varies, with the maximal turnover at about the time histone RNA level peaks. A half-life of 1.5 hr at 12 hr of development is estimated. Change in transcriptional rate per nucleus, increase in cell number, and probably a change in mRNA stability as well are therefore involved in the control of histone mRNA levels in the early embryo.

Adenosine Triphosphate↗
PubMed1983

Reactions of methylnitrosourea, epichlorohydrin, styrene oxide and acetoxyacetylaminofluorene with polyamino acids.

Radioactive methylnitrosourea, epichlorohydrin, styrene oxide, and N-acetoxy-2-acetylaminofluorene were reacted with 14 different polyamino acids in vitro, to determine the relative reactivity of the functional groups in amino acids. All the carcinogens reacted preferentially with polycysteine and much less with polyhistidine. Reaction was also noted with polylysine, polymethionine and polyarginine, as well as with DNA. Epichlorohydrin and styrene oxide reacted also with polyserine. Methylnitrosourea and N-acetoxy-2-acetylamino-fluorene reacted relatively more with polyhistidine as compared with the epoxides. Polycysteine, polyhistidine and polylysine were more reactive towards styrene oxide at pH 8 than at pH 6.

2-Acetylaminofluorene↗
PubMed1983

Sites of reaction of propane sultone with guanosine and DNA.

Propane sultone was reacted with guanosine and DNA at pH 6--7.5, and te reaction products were purified by Sephadex chromatography and h.p.l.c. The products were characterized by u.v. spectra, loss of tritium from the C-8 position and dissociation properties. The main product was shown to be an N-7-alkyl guanosine, accounting for greater than 90% of the total product. Similar evidence suggested that two of the minor adducts were N-1 and O6 alkyl derivatives, accounting for approximately 1.6 and 0.5% of the total adduct, respectively. N-7 and N-1 alkyl guanine were also detected in DNA reacted with propane sultone.

Alkylation↗
PubMed1983

Embryotoxic effects of acrolein, methacrylates, guanidines and resorcinol on three day chicken embryos.

Acrolein, four methacrylates, two guanidine compounds and resorcinol were tested for embryotoxicity on three day chicken embryos. The most potent chemical was acrolein, with the ED50 0.05 mumol per egg for the total effect, including deaths and malformations. The substances next in potency were N,N'-di-o-tolyl-guanidine and N,N-diphenylguanidine, with ED50 values 0.17 and 0.20 mumol per egg, respectively. Resorcinol and the methacrylates had ED50 values ranging from 2.4 to 22.0 mumol per egg. Acrolein, diphenylguanidine, tetrahydrofururylmethacrylate and trimethylolpropanetrimethacrylate caused the largest amounts of malformed embryos.

Acrolein↗
PubMed1983

Correlations of alkylating activity and mutagenicity in bacteria of cytostatic drugs.

Alkylating activity of cytostatic drugs was studied in relation to their mutagenicity and toxicity in E. coli WP2 uvrA. Four classes of directly acting cytostatic drugs were studied: nitrogen mustards (nitrogen mustard, melphalan, chlorambucil and phosphoramide mustard, a metabolite of cyclophosphamide), ethyleneimine derivatives (Thio-TEPA, TEPA and triethylenemelamine), busulfan, and halogenated nitrosoureas. The reference compounds included methyl methanesulfonate, ethyleneimine and methylnitrosourea. Guanosine alkylation was determined by fluorometry. The rate of guanosine and nitrobenzylpyridine alkylation agreed well. Nitrogen mustard derivatives and triethylenemelamine were the most potent alkylating agents among the cytostatic drugs; nitrogen mustard was 5 to 10 times more active than methyl methanesulfonate. Ethyleneimine derivatives, busulfan and the nitrosoureas were relatively weak alkylating agents. Nitrogen mustard and triethylenemelamine were the most potent mutagens to bacteria; they were also among the most toxic drugs studied.

Alkylating Agents↗
PubMed1983

Spontaneous abortions in an industrialized community in Finland.

Spontaneous abortions were analyzed in an industrialized Finnish community according to the occupation and workplace of both the women and their husbands. Information about spontaneous abortions and births was obtained from the hospital discharge register, and data about the women and their families were collected from census files. When compared with all women employed outside the home, women who worked at a textile plant (factory A, a clothing manufacturer) had an increased rate of spontaneous abortion (16.7 per cent vs 11.4 per cent). The rate of spontaneous abortions among women employed at factory A differed according to the husband's workplace. The odds ratio for women employed at factor A whose husbands worked at a large metallurgical factory was 3.8, whereas the odds ratio for women whose husbands worked elsewhere was 1.2. Between 1973 and 1976, the rate of spontaneous abortions in this town was consistently lower for the summer period. (May-August) than for the other periods of the year.

Abortion, Spontaneous↗
PubMed1983

Embryotoxic effects of phtalic acid derivatives, phosphates and aromatic oils used in the manufacturing of rubber on three day chicken embryos.

Several chemicals that are used for manufacturing of rubber were tested for embryotoxicity on three day chicken embryos. Cyclohexylthiophtalimide was the most potent of the chemicals, with an ED50 value for the total embryotoxic effect 0.04 mumol (10 micrograms) per egg. Phtalic anhydride was about ten times less potent, having the total ED50 for total embryotoxicity 0.38 mumol (56 micrograms) per egg. Two esters of phtalic acid, dibutylphtalate and butylbenzylphtalate, instead, were relatively impotent, with ED50 values of about 33 mumoles and 27 mumoles per egg, respectively. Two phosphates, tricresylphosphate and synthetic arylphosphate, were not potent embryotoxic agents in the chick embryos. They had ED50 values of 7.0 mumoles (2.6 mg) per egg and 9.5 mg per egg, respectively. Sodium phosphate (NaH2PO4) had the ED50 11 mumoles per egg. Three types of oils were tested, too. A mixture known as "highly aromatic oils" was the most potent, with the ED50 31 micrograms per egg. "Low aromatic, paraffin base oils" was the next potent, with the ED50 87 micrograms per egg, while "naphtenic oils" had the ED50 480 micrograms per egg. Cyclohexylthiophtalimide and phtalic anhydride caused malformations at high frequency. The oils and tricresylphosphate appeared to be efficient teratogens under the experimental conditions used.

Abnormalities, Drug-Induced↗
PubMed1983

Toxicity of rubber chemicals towards three-day chicken embryos.

Three-day chicken embryos were exposed to 80 different rubber chemicals dissolved in either acetone or water. The following classes of chemicals were studied: thiurams, dithiocarbamates, thioureas, benzothiazoles, benzenesulfohydrazide, dithiodimorpholine, amines, acrylates, guanidines, resorcinol, phthalates, adipates, phosphates, oils, peroxides, heavy metal salts, and sodium nitrite. Dose-response curves and median lethal doses (LD50) or median effective doses (ED50) were calculated for mortality in 2 d after the treatment, for total mortality in 11 d after the treatment, and for the total effect, including deaths and malformations 11 d after the treatment, when the test was finished. Sixteen of the chemicals had no effect on the embryos when injected into the air chamber. Incomplete and irregular dose-response curves for the total effect were obtained with 13 of the chemicals. For them, the ED50 could be calculated. Among the remaining 51 chemicals, the most potent were the dithiocarbamates and cadmium and copper acetates, with the total effect ED50 from 2.4 to 160 nmol/egg. Other chemicals that had an ED50 smaller than 100 nmol/egg were thiurams, cyclohexylthiophthalimide, acrolein, and dithiodimorpholine. The majority of the chemicals had an ED50 between 100 nmol/egg and 10 mumol/egg. The least potent were sodium nitrite and methylmethacrylate with an ED50 of 22 mumol/egg. All the 64 embryotoxic chemicals caused malformations with only one exception (dibutylthiourea). The maximum observed frequencies of malformed embryos varied from 3 to 100% of the treated embryos.

Abnormalities, Drug-Induced↗