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Biomedical subjects

K Hemminki

Publications and source records attributed to K Hemminki.

At least 379 records · Page 21Linked to original sources
PubMed1985

A study of occupational exposure to antineoplastic drugs and fetal loss in nurses.

In a case--control study, we examined the relation between fetal loss and occupational exposure to antineoplastic drugs in nurses in 17 Finnish hospitals. The pregnancies studied occurred in 1973 through 1980 and were identified using three national sources: the Central Register of Health Care Personnel, the Hospital Discharge Registry, and policlinic data. Each nurse with fetal loss was matched with three nurses who gave birth. Data on health and exposure were obtained by self-administered, mailed questionnaires; a response rate of 87 per cent was achieved after three mailings. A statistically significant association was observed between fetal loss and occupational exposure to antineoplastic drugs during the first trimester of pregnancy: odds ratio = 2.30 (95 per cent confidence interval, 1.20 to 4.39). Analyses suggested associations between fetal loss and cyclophosphamide, doxorubicin, and vincristine, although the independent effect of each individual drug could not be specifically identified, since many nurses reported handling more than one of these agents. The results of this study, combined with existing data on animals and human beings, suggest that caution be exercised in the handling of these valuable drugs.

Abortion, Spontaneous↗
PubMed1985

Spontaneous abortions among women employed in the plastics industry.

A matched case-control study was done to analyze whether certain occupational exposures in the plastics industry were related to the risk of spontaneous abortions. Information on spontaneous abortions (cases) and births (controls) was obtained from the hospital discharge register; data on occupational exposures were obtained from the occupational health services of the workplaces. No increased risk of spontaneous abortions was observed among workers processing polymerized plastics or heated plastics made of vinyl chloride or of styrene. Owing to the low statistical power of the study, only strong effects can be ruled out. The odds ratio for workers actually processing polyurethane was increased (1.9, not statistically significant), and that for all workers in polyurethane-processing factories was significantly increased (3.0, p = 0.02). The finding needs to be investigated further in future studies.

Abortion, Spontaneous↗
PubMed1985

Extrapolation of the evidence on teratogenicity of chemicals between humans and experimental animals: chemicals other than drugs.

Epidemiologic literature regarding the possible association between malformations and 23 exposures or occupations other than pharmaceutical products, was analysed. The qualitative level of scientific evidence was classified into four categories: high (ethanol, methylmercury, PCBs, laboratory work), limited (anesthetic gases, carbon monoxide), low (hexachlorophene, LSD, nitrous oxide, smelter work, tobacco), and inadequate (all other exposures). Human data for exposures belonging to categories "high" and "limited" were quantitatively compared to results of animal teratogenicity tests of the relevant chemicals. Ethanol, methylmercury, and PCBs have caused malformations in experimental animals, and the effective doses have ranged from 0.2 to 8.0 times the effective human doses. Ethanol and PCBs caused similar types of lesions in some animal species as have been observed in humans.

Abnormalities, Drug-Induced↗
PubMed1985

Occupational exposure to anticancer drug--potential and real hazards.

Many anticancer agents have been shown to be mutagenic, teratogenic and carcinogenic in experimental systems and second malignancies are known to be associated with several specific therapeutic treatments. Anticancer agents thus represent a class of occupational carcinogens, the handling of which should involve no unnecessary exposure. The available methodologies to detect possible exposures from ambient air and from biological samples are discussed, and the published data on results are reviewed. Analytical methods are available for the detection of most frequently used anticancer drugs from all groups, i.e., alkylating agents, mitotic inhibitors, antimetabolites and antibiotics. The ambient samples taken from sites of admixture of cytostatics have often shown detectable, but low concentrations of anticancer agents. Urine samples from patients under chemotherapy as well as from personnel handling the drugs occupationally in hospitals have been analyzed both chemically and for excreted mutagenicity. Both cisplatin and cyclophosphamide have been detected in the urine of patients; furthermore, cyclophosphamide was observed in the urine of nurses who formulate and deliver this drug. Urinary mutagenicity assays have given both positive and negative results in various groups of nursing and pharmacy personnel. Cytogenetic methods have, likewise, been applied for monitoring purposes. Most of the available data concerns chromosome aberrations (CA) or sister-chromatid exchanges (SCE) induced in peripheral blood lymphocytes of patients under chemotherapy. A few studies on groups occupationally exposed to anticancer drugs have given positive results, but also negative reports have appeared for these same cytogenetic parameters. No studies are as yet available on the possible carcinogenic effects of occupational handling of anticancer drugs. Two recent case-referent studies among hospital personnel have pointed to slightly increased risks of disorders in pregnancy outcome; one of the studies has shown an excess of spontaneous abortions and other malformations in children of females with a history of work with anticancer agents.

Abnormalities, Drug-Induced↗
PubMed1985

Data on the carcinogenicity of chemicals in the IARC Monographs programme.

Data were extracted from IARC Monographs volumes 1-38 on chemicals and exposures for which some data on carcinogenicity in humans, or sufficient evidence of carcinogenicity in experimental animals existed. In all, 288 chemicals, industrial processes and complex mixtures fulfilled these criteria. For 30 chemicals or mixtures of chemicals, and nine industrial processes, there was sufficient evidence of carcinogenicity in humans; and for 63 chemicals and mixtures of chemicals and for five industrial processes, there was evidence that these exposures were probably carcinogenic to humans. For 61 chemicals or groups of chemicals and six industrial processes or occupations, no evaluation of carcinogenicity to humans could be made. For 115 chemicals there is sufficient evidence of carcinogenicity to experimental animals, but no epidemiological data are available. Publications not earlier referred to on the carcinogenicity of these chemicals and exposures were found for approximately 70. A call is made for further information on these exposures with a view to updating the IARC Monographs.

Animals↗
PubMed1985

Spontaneous abortions and malformations in the offspring of nurses exposed to anaesthetic gases, cytostatic drugs, and other potential hazards in hospitals, based on registered information of outcome.

Nurses working in selected departments of general hospitals in Finland were collected from a central register on health personnel in Finland. Using the Hospital Discharge Register and the Register of Congenital Malformations, case nurses were selected who had had a spontaneous abortion (N = 217) or a malformed child (N = 46) between the years 1973 and 1979. Controls consisted of three nurses who had had a normal birth; the control nurses were matched for age and hospital of employment. Information on exposure in the first trimester of pregnancy was sought through the head nurses of the hospitals. No significant increase in risk of spontaneous abortion or of malformation was observed after exposure to anaesthetic gases (odds ratio for spontaneous abortion 1.2), sterilising gases and soaps, or x-rays. Handling of cytostatic drugs did not affect the frequency of spontaneous abortion but was associated with malformations in the offspring. The odds ratio, based on eight cases, was 4.7 (p = 0.02) when the logistic model was adopted. The results suggest that the exposures investigated, other than cytostatic drugs, do not cause a strong reproductive risk. Further studies are needed, particularly on cytostatic drugs.

Abnormalities, Drug-Induced↗
PubMed1985

Detection of benzo(a)pyrene:DNA adducts in human white blood cells.

Metabolic activation of benzo(a)pyrene (BP) to its ultimate carcinogenic form, 7 beta, 8 alpha-diol-9 alpha, 10 alpha-benzo(a)pyrene epoxide (BPDE), and the binding of BPDE to DNA are important steps in BP carcinogenicity in experimental animals. Since people of certain occupations are exposed to high concentrations of BP, we have used enzyme-linked immunosorbent assay and ultrasensitive enzymatic radioimmunoassay to measure BPDE:DNA adducts in white blood cells from 2 of these occupational groups. Seven of 28 samples from roofers and 7 of 20 samples from foundry workers were positive for BPDE:DNA adducts (range, 2 to 120 fmol BPDE/50 micrograms DNA). In a group of nine volunteers without these industrial exposures to BP, the two positive DNA samples were from cigarette smokers. Control DNA obtained from human lymphocyte cell line RPMI 4265 was negative. These results indicate that the metabolic activation of BP and formation of BPDE:DNA adducts occurs in humans.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1985

Binding of metabolites of cyclophosphamide to DNA in a rat liver microsomal system and in vivo in mice.

The stability of phosphoramide mustard, a metabolite of cyclophosphamide was studied at pH 7.2 and 37 degrees C using 31P nuclear magnetic resonance. The phosphorus signal of phosphoramide mustard disappeared with a half-life of 8 min indicating rapid conversion to other species. The final product, inorganic phosphate, appeared with a half-life of 105 min indicating that phosphoramide mustard was easily dephosphoramidated. A rat liver microsomal system was used to study the binding of [chloroethyl-3H]cyclophosphamide to DNA. DNA was hydrolyzed in 0.1 N HCl:0.5 N NaCl at 80 degrees C for 20 min, conditions known to convert phosphoramide mustard to nornitrogen mustard with liberation of the phosphoramide residue. After such treatment three adducts were detected by high-performance liquid chromatography using several elution systems. They were all 7-substituted guanine adducts of nornitrogen mustard; two were monoalkylation products with an intact [N-(2-chloroethyl)-N-[2-(7-guaninyl)ethyl]amine] or an hydroxylated mustard arm [N-(2-hydroxyethyl)-N-[2-(7-guaninyl)ethyl]amine]; the third adduct was a cross-linked product [N,N-bis [2-(7-guaninyl)ethyl]-amine]. The relative abundance of these adducts depended on the length of the microsomal incubation. After 2 h, N-(2-chloroethyl)-N-[2-(guaninyl)ethyl]amine was the main product but after 6 h N-(2-hydroxyethyl)-N-[2-(7-guaninyl)ethyl]amine was most abundant, and at this time the cross-linked product represented 12% of the total adducts. The adducts in DNA depurinated readily and after 24 h at pH 7.0 and 37 degrees C 70% of them had been liberated. The rate of depurination was decreased in the presence of 0.5 N NaCl. After short-term depurination in 0.1 N HCl at 25 degrees C the primary alkylating species was phosphoramide mustard rather than nornitrogen mustard. In in vivo studies mice were given injections i.p. of 100 microCi of cyclophosphamide. Maximal levels of radioactivity had been incorporated into DNA between 2-7 h after injection; the specific activity of DNA from the kidney and lung exceeded that from the liver. While the level of radioactivity found in kidney DNA was rapidly reduced the rate of fall was lower in the lung. Between 24 and 72 h the specific activity of lung DNA exceeded that of kidney and liver DNA by a factor of 3:8. Lung is the principal target tissue for tumor formation in mice after an i.p. injection.

Animals↗
PubMed1984

Sites of reaction of glutaraldehyde and acetaldehyde with nucleosides.

Glutaraldehyde, a dialdehyde, was reacted with ribonucleosides and deoxyribonucleosides and the products were purified by high-performance liquid chromatography (HPLC). Multiple reaction products were identified with cytosine- and purine-containing nucleosides. The products were labile, but spectroscopic evidence indicated that exocyclic amino groups were involved. Similar reactions were seen with acetaldehyde and butyraldehyde, monofunctional aldehydes. After reduction, one of the acetaldehyde-guanosine adducts was assigned the structure N2-ethylguanosine.

Acetaldehyde↗
PubMed1984

Reactions of ethyleneimine with guanosine and deoxyguanosine.

Ethyleneimine was reacted with guanosine in aqueous medium and the products were purified by Sephadex G-10 and high-performance liquid chromatography (HPLC). Two products were identified by UV-spectroscopy: imidazole-ring opened 7-alkylguanosine and 1-alkylguanosine, accounting for 80% and 14% of all adduct radioactivity, respectively. When the incubation with ethyleneimine and guanosine or deoxyguanosine was carried out at pH 6.0 for 1 h intact 7-alkylation products were detected. The half-life of imidazole ring opening of 7-alkylguanosine was 11, 5 and 2.8 min at pH-values 7.0, 7.7 and 8.0, respectively, as measured fluorometrically at 25 degrees C. The respective half-life of alkylated deoxyguanosine was 21 min at pH 7.7. The half-life of depurination of alkylated deoxyguanosine was 42 min at pH 6.0 and 25 degrees C.

Aziridines↗
PubMed1984

Embryotoxic effects of eight organic peroxides and hydrogen peroxide on three-day chicken embryos.

Nine peroxides were tested for embryotoxicity in 3-day chicken embryos using the air-chamber method. The potencies were expressed by the ED50 for the total embryotoxic effect of the chemicals, including deaths and malformations, up to Day 14 of the incubation. The range of the ED50's was from 0.13 to 2.7 mumoles per egg and the order of the potencies was as follows: cyclohexanoneperoxide greater than cumolhydroperoxide greater than ethylmethylketoneperoxide greater than dibenzoylperoxide greater than acetylacetoneperoxide greater than perbenzoic acid-tert-butylester greater than dicumylperoxide greater than dilauroylperoxide greater than hydrogen peroxide. All nine peroxides caused malformations at a moderate frequency. The maximum percentage of malformed embryos of the treated varied from the 16% of perbenzoic acid-tert-butylester to the 56% of dicumylperoxide. The high percentage caused by the latter could, however, result from slow diffusion of high lethal doses from the air chamber to the embryo.

Abnormalities, Drug-Induced↗
PubMed1984

Formation of phosphodiesters in thymidine monophosphate by styrene oxide.

Three products were isolated by high-performance liquid chromatography (HPLC) from the reaction between thymidine-5'-monophosphate (TMP) and styrene oxide in aqueous solution. None of the products was digested by alkaline phosphatase, but each was digested by vernom phosphodiesterase. The digestion products were identified by their mobility in HPLC and UV-spectra as phenylethylene glycol, thymidine, TMP, and hydroxyethylphenyl phosphoric acid, of which phenylethylene glycol and TMP were most abundant.

Alkaline Phosphatase↗
PubMed1984

Reaction products of styrene oxide with guanosine in aqueous media.

Styrene oxide was reacted with guanosine in fully aqueous conditions, and the products were purified by cation exchange chromatography and h.p.l.c. The products were characterized by u.v. and mass spectra, loss of tritium from the C-8 position and dissociation properties. About 90% of the total product was identified, of which 57, 28 and 15% were assigned to N-7, N2 and O6 adducts. The two diastereomers of beta-substitution accounted for 53% of the N-7 adducts, while the two alpha-substitutions accounted for the remaining 47%. Two species of N2 and O6 products were also isolated but their substitution pattern was not established.

Chemical Phenomena↗
PubMed1984

Parental occupational exposure and spontaneous abortions in Finland.

Spontaneous abortions were analyzed by the occupational exposure of women and their husbands, with data from the Finnish hospital discharge register and the national census. The occupations were grouped according to presumed exposure into seven categories: exposure to solvents; automobile exhaust fumes; polycyclic aromatic hydrocarbons; other chemicals; metals; textile dust; and animal microorganisms. The relative risks of spontaneous abortion were estimated with logistic regression analysis to adjust for potentially confounding factors. The broad exposure categories appeared, at most, to be weak risk factors of spontaneous abortion, because the relative risks of abortion were not significantly increased in any of the parental exposure groups. The analysis of detailed occupational categories showed some female and male occupations with an increased risk. The observations of increased risk related to laboratory work support earlier findings. The high number of textile occupations with increased risk is also worth noting, and further investigations are necessary to confirm whether this is due to occupational hazards or other factors.

Abortion, Spontaneous↗
PubMed1984

Alkylation of guanosine by phosphoramide mustard, chloromethine hydrochloride and chlorambucil.

Guanosine was reacted in vitro with phosphoramide mustard, chloromethine hydrochloride, and chlorambucil. The products were isolated by HPLC and characterized by UV and fluorescence spectroscopy, and C-8 tritium exchange. The primary products were 7-alkylguanosines according to such evidence. Phosphoramide mustard had 1/10 of the apparent alkylation activity of two other mustards. The primary 7-alkylguanosines were unstable at pH 7.4 and 37 degrees; t1/2 were 3 min. for chloromethine hydrochloride, 2.7 hrs for chlorambucil and 3.0 hrs for phosphoramide mustard. Both dechlorination at the unbound arm of the mustard and imidazole ring opening og guanosine appeared to account for such instability.

Alkylation↗