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Biomedical subjects

K Norpoth

Publications and source records attributed to K Norpoth.

At least 37 records · Page 2Linked to original sources
PubMed1993

[Polychlorinated biphenyls (PCBs) and reproduction disturbances].

A review of the impact of chlorinated biphenyls (PCBs) on reproduction is presented. PCBs are able to pass the placenta; accumulation in offspring is mainly achieved by breast feeding. Disturbances of fertility and embryotoxicity were detected in animals; teratogenicity without maternal toxicity was only observed in mice. In animal experiments disturbances of fetal and postnatal development were detected as well as in human studies. Neurotoxicity was observed even at low-level exposures in monkeys, which are most comparable to humans because of the development of the same clinical symptoms. Technical PCBs which are dominating in occupational and environmental exposure until now must be judged as toxic for reproduction: dermal exposure (especially in accidents) should be considered as an important route of exposure beside inhalation. Work to list possible PCB exposure risks and to develop ways to reduce these risks are necessary now.

Abnormalities, Drug-Induced↗
PubMed1992

Concentrations of tetrachloroethene in blood and trichloroacetic acid in urine in workers and neighbours of dry-cleaning shops.

Tetrachloroethene concentrations in blood and trichloroacetic acid concentrations in urine were determined--primarily over the course of a week--for 29 persons living in the vicinity of dry-cleaning shops. The mean levels of tetrachloroethene increased during the week. In some neighbours concentrations were exceeding the German biological threshold limit value for tetrachloroethene (1000 micrograms/l blood), persisting over the whole week in one case. The concentrations of tetrachloroethene in blood depended on the floor and the construction type of the building where these people were living, but not of the type of system used in the dry-cleaning shops. 5 of 12 dry-cleaners were found to have tetrachloroethene levels exceeding the German biological threshold limit value, some of them by a considerable amount.

Environmental Exposure↗
PubMed1992

Investigations of the frequency of DNA strand breakage and cross-linking and of sister chromatid exchange frequency in the lymphocytes of female workers exposed to benzene and toluene.

Peripheral lymphocyte DNA damage as measured by the method of alkaline filter elution and the frequency of sister chromatid exchange (SCE) in lymphocytes was investigated for a group of 20 female workers of a shoemaking plant who were exposed to benzene and toluene, primarily below the German threshold limit value of 5 and 100 p.p.m. respectively; the results were compared with those from a control group. In the female workers significantly raised (P less than 0.05) SCE values were found. The relative DNA elution rate through polycarbonate filters was significantly increased (P less than 0.001). The elution rate through polyvinylidene fluoride (HVLP) filters showed a tendency to increase (P = 0.052), which must be interpreted as indicating increased DNA strand breakage. The SCE rates of the female workers were significantly correlated (P less than 0.01) with the relative DNA elution rate through HVLP filters. There was no correlation with the actual benzene and toluene uptake measured by personal air monitoring. Four months after cessation of work, DNA strand breakage decreased significantly (P less than 0.05) in blood samples of six reinvestigated female workers.

Adult↗
PubMed1992

Investigations of the frequency of DNA strand breakage and cross-linking and of sister chromatid exchange frequency in the lymphocytes of patients with multiple myeloma undergoing cytostatic therapy with melphalan and prednisone.

An investigation was made of 17 patients with multiple myeloma using the method of alkaline filter elution for the detection of DNA damage and the determination of sister chromatid exchange (SCE) frequency in peripheral lymphocytes during a course of chemotherapy with melphalan and prednisone. We were able to detect elevated SCE frequencies in pretreated patients that approximately doubled during the therapeutic cycle. An appreciable level of DNA cross-linking was detected by alkaline filter elution; DNA cross-linking scarcely increased during a course of chemotherapy. The increase in the SCE frequency during the first therapy cycle was even greater in the case of patients with newly diagnosed multiple myelomas. The results obtained by alkaline filter elution and measuring SCE frequencies suggest that these techniques are suitable as methods in molecular epidemiology, especially if applied to persons who are chronically exposed to cytostatic drugs. Whether or not the methods could be valuable in evaluating therapy response needs further investigation.

Aged↗
PubMed1992

Incidence of bladder cancer in a cohort of workers exposed to 4-chloro-o-toluidine while synthesising chlordimeform.

Between 1982 and 1990 seven cases of bladder cancer were detected in a group of 49 workers who were synthesising chlordimeform from 4-chloro-o-toluidine. Latency periods ranged from 15 to 23 years. The incidence of bladder tumours in this group was significantly higher than that of the cancer registers of the former GDR, Saarland, and Denmark by factors of 89.7, 53.8, and 35.0 respectively. This provides further evidence that monocyclic aromatic amines such as 4-chloro-o-toluidine may be carcinogenic in humans.

Adult↗
PubMed1992

[Experiences with alkaline filter elution for the detection of DNA damage by genotoxic compounds].

In biological effect monitoring the alkaline filter elution is a suitable method to detect DNA strand breakage and cross-linking in peripheral blood lymphocytes. We applied this method to three groups of workers occupationally exposed to carcinogens: n = 39 welders with exposure to chromium and nickel, n = 20 female shoemakers with exposure to benzene and n = 25 disinfectors in hospitals with exposure to ethylene oxide. In comparison to standardised control groups our results must be interpreted as indicating an increased rate of DNA cross-linking in welders and disinfectors whereas the female shoemakers showed an increased rate of DNA strand breakage. The differences between the results of the exposed groups and the stratified control groups were significant in most cases. We could reexamine 6 shoemakers 4 months after cessation of exposure to benzene; at this moment the results were indicating a clear decrease of the DNA strand breakage. Therefore the method of alkaline filter elution seems to be a valuable tool in biological effect monitoring of groups occupationally or environmentally exposed to carcinogens, especially if the exposure is low, but persistent over a long period.

Benzene↗
PubMed1991

Investigations of the frequency of DNA strand breakage and cross-linking and of sister chromatid exchange in the lymphocytes of electric welders exposed to chromium- and nickel-containing fumes.

A total of 39 electric welders exposed to chromium and nickel were compared with 18 controls standardized for age, smoking habits and sex with respect to the frequency of sister chromatid exchange (SCE) and of DNA strand breakage and cross-linking (measured by the method of alkaline filter elution) in their blood lymphocytes. A significant correlation was found between the frequency of SCE and of individual DNA strand breakage and the concentration of chromium in the urine. Less DNA from the welders than from the control group was eluted through the two filter types used (polycarbonate and polyvinylidene fluoride filters). This must be interpreted as resulting from the presence of DNA-protein cross-links, which has the secondary effect of leading to a relative reduction in the measurable frequency of strand breakage amongst the welders. The present results are in good agreement with in vitro and in vivo investigations that confirm the importance of DNA-protein cross-links for the carcinogenic effect of chromium.

Air Pollutants, Occupational↗
PubMed1991

Mutagenic activity of some newly synthesized cytostatic 1-(2-chloroethyl)-4-arylacyl-1-nitrososemicarbazides in the Salmonella/mammalian microsome assay.

Five experimental anti-leukemic agents, 1-(2-chloroethyl)-4-arylacyl-1-nitrososemicarbazides, were synthesized and tested for genotoxicity in the Salmonella/mammalian microsome assay. No strong mutagenic activity could be detected when tested with the S. typhimurium TA98. A clear dose-dependent base-pair-substitution mutagenic activity was observed with each compound when the tester strain TA100 was used with or without metabolic activation. The genotoxicity of the unsubstituted substance was similar to that of the known mutagenic cytostatic drugs, lomustin and carmustin, and was stronger than the mutagenicity of each substituted derivative.

Antineoplastic Agents↗
PubMed1990

Comparative carcinogenicity of cigarette mainstream and sidestream smoke condensates on the mouse skin.

The direct carcinogenic effects of sidestream (SS) and mainstream (MS) smoke condensates of a filtered commercial brand of blond cigarettes were compared using a lifetime mouse skin tumorigenicity assay on female NMRI mice. Each cigarette was smoked by a smoking machine under the standard conditions, and the separately collected SS and MS smoke condensates were extracted with acetone/methanol as described elsewhere. These were tested for carcinogenicity on an area of 1-1.5 cm shaved skin of mice on the lower back. The mice were treated with half of each dose (5, 10 or 15 mg) twice a week, for only 3 months. No substance was used as promoter or as an additional initiator of carcinogenicity. No statistically significant difference was found when the life spans of MS-treated and untreated animals were compared. In contrast, the life spans of SS-treated mice were significantly (P less than 0.01) shorter than those of MS-treated animals or those of all three negative control groups together. The observed carcinogenic effects were based on tumours and lesions found only on the site of application of the test material. Of 210 mice (effective number, 129) serving as the negative controls, 3 developed skin lesions but no tumours. Of 210 MS-treated mice (effective number, 177), 7 developed tumours (4 malignant and 3 benign) and 35 had a uniform type of precancerous skin lesions. The numbers of tumours or lesions were not increased dose-dependently. Of 210 SS-treated animals (effective number, 182), 30 developed tumours (16 malignant and 14 benign) and 56 had a uniform type of precancerous skin lesion. The initiation of these latter lesions was found to be dose-dependent (P less than 0.001). The SS-treated animals developed two to six times more skin tumours than the MS-treated mice. Comparing the negative controls with the MS- or SS-treated animals, the overall carcinogenic effect observed was statistically significant. Comparing the MS- with SS-treated animals, the overall carcinogenic effect of SS was much higher than that of MS (P less than 0.001).

Animals↗
PubMed1990

Release of mutagens after chemical or microbial degradation of beech wood lignin.

The microbial or chemical degradation of lignin from untreated samples of beech wood dusts (Fagus silvatica) resulted in the release of different mutagenic responses in the Salmonella/mammalian plate incorporation assay. In the first experiment using chemical degradation of lignin, dust samples were pre-extracted using acetone-water; the lignin portions were degraded into simpler compounds which were further fractionated on a Sephadex-LH20 column. The compounds isolated from the second phase of Sephadex, representing substances with a 3-4 ring structure and/or those of the same molecular weight, were highly mutagenic towards Salmonella typhimurium TA100 in the presence of metabolic activation. These substances were also active to some extent in strain TA1537 both in the presence and absence of Aroclor-induced rat liver homogenates. In contrast, no direct- or indirect-acting mutagenicity was found when testing with strains TA97 and TA98. Strain TA1535 responded positively only to direct-acting mutagens in the fraction tested. The mutagenic fraction was found to be toxic to the cells when tested in a histidine-rich medium. Repurification of this mutagenic fraction, using silica-gel column chromatography, revealed much higher mutagenic activity than the test material towards strain TA100. In the second pilot experiment, Phanerochaete chrysosporium and Chaetomium globosum, which are known for their ability to degrade lignin, were each incubated with wood dusts in a mixture of physiological saline and nutrient broth for either 3 or 30 days. Significant mutagenic activity was observed with the dust extract after incubation with Ph. chrysosporium but not with Ch. globosum which is a known degrader of beech lignin. These results are discussed regarding hypotheses on the carcinogenicity of beech wood dusts.

Animals↗
PubMed1989

Urinary and faecal excretion of pyrene and hydroxypyrene by rats after oral, intraperitoneal, intratracheal or intrapulmonary application.

The urinary and faecal excretion of pyrene and 1-hydroxypyrene after oral (53.4%), intraperitoneal (3.1%), intratracheal (30-37%) and intrapulmonary application (0.003%) to rats has been determined by means of gas chromatography/mass spectrometry and the excretion rates were found to depend on the mode of application. With regard to the low urinary excretion rates, 1-hydroxypyrene seems not to be very suitable as a biological marker for PAH exposure to man.

Animals↗
PubMed1989

Cancer epidemiology of woodworking.

The literature published between 1965 and 1989 on the cancer epidemiology of woodworking in furniture industries and carpentry shops in 17 countries is reviewed. Included are some unpublished data obtained through personal communication with epidemiologists or collected from doctoral dissertations. Of 5,785 cases with sino-nasal cancers, about 23% were found to be woodworkers. Dusty jobs, especially wood processing using high-speed machines, are mainly associated with the enhanced incidence of nasal adenocarcinomas. The latency periods of the latter tumors ranged from 7 to 69 years in five European countries. A variety of neoplasias of the respiratory, digestive, and urinary tracts as well as the hemopoietic and lymphatic systems, including Hodgkin's disease are reported to be significantly associated with occupational exposure to wood dust. These data suggest that the exposure to some types of wood dust might cause a systemic rather than local neoplastic disorder.

Australia↗
PubMed1989

The excretion of chlorophenylmercapturic acid, chlorophenols and a guanine adduct in the urine of chlorobenzene-treated rats after phenobarbital pretreatment.

Chlorobenzene (CB) was administered to male Wistar rats. Twenty-four-hour urine samples were collected over a period of 7 days. p-Chlorophenylmercapturic acid, chlorophenols and a guanine adduct were determined by chromatographic methods. The excretion pattern of p-chlorophenyl-mercapturic acid did not seem to be significantly affected by phenobarbital. To analyze for the chlorophenols and guanine adducts, diluted urine was subjected to cation exchange chromatography using UV-detection. Fractions were found containing chlorophenols and a compound showing chromatographic properties similar to those of the synthetic N7-phenylguanine. The results of the HPLC analyses suggested the presence of a guanine adduct excreted on days 1 and 2 and between days 4 and 6 post-administration. There were no compounds detected which were identical with p-, m- or o-isomers of N7-chlorophenylguanine. The excretion of p- and m-chlorophenols by phenobarbital-pretreated animals was twice as high as that in untreated rats. A 4-fold increase was detected for o-chlorophenol. It is assumed that it is mainly direct hydroxylation that can be induced by phenobarbital. Dehalogenated phenolic metabolites may be capable of covalent binding to DNA.

Acetylcysteine↗
PubMed1989

Determination of S-phenylmercapturic acid in the urine--an improvement in the biological monitoring of benzene exposure.

In an inhalation study rats were exposed to different doses of benzene, ranging from 1 to 500 p.p.m. The urine was sampled during the inhalation period of 8 h and for 24 h after exposure. S-Phenylmercapturic acid (S-PMA) in the urine was determined by amino acid analysis. Phenol was measured by gas chromatography/mass spectrometry. In both cases the correlation between benzene uptake and the excretion of the urinary metabolites was significant at the level of P = 0.01. The same significant correlation (P = 0.01) was demonstrable after i.p. administration of benzene at doses between 0.7 and 140.0 microliters/kg body weight. In the case of two collectives of workers who were exposed to air concentrations of up to 0.15 p.p.m. for 8 h and of up to 1.13 p.p.m. for 12 h respectively, the amount of S-PMA in the first urine samples after the shift was significantly higher than in samples collected at the beginning of the shift (P = 0.01). In the first collective the mean values and the standard deviations of the S-PMA concentrations in the samples at the beginning of the shift were 12.0 +/- 16.7 compared with 48.5 +/- 64.5 micrograms/g creatinine at shift end. In the second collective they were 25.1 +/- 25.1 compared with 70.9 +/- 109.2 micrograms/g creatinine. The level of significance of the difference between the concentration values of S-PMA at the beginning and end of the shift was P = 0.01. The phenol concentration did not differ significantly. These results suggest that S-PMA can be regarded as a useful indicator for monitoring individuals and collectives exposed to benzene at levels even less than 1 p.p.m.

Acetylcysteine↗
PubMed1989

The mouse-skin carcinogenicity of a mutagenic fraction from beech wood dusts.

A life-time mouse-skin carcinogenicity assay was conducted using female NMRI mice to evaluate the possible direct carcinogenic activity of a mutagenic fraction isolated from beech wood dusts. The samples of untreated beech wood dusts were extracted with methanol at pH3 and were purified from the inhibitory compounds toxic to bacteria, using silica-gel column chromatography. The fraction obtained after passing through the column was tested for mutagenicity in the Ames assay employing Salmonella typhimurium TA100 in the presence of Aroclor-treated rat-liver-S9. Using acetone as the vehicle, this mutagenic fraction was tested for carcinogenicity on an area of 1-1.5 cm shaved skin of mice on the lower back. The mice were treated with half of each dose, twice a week, for only 3 months. The total doses applied per week were 2.5, 5, 7.5 or 10 g equivalent dust/mouse. No substance was used as promoter. No statistically significant difference was found when the life spans of treated and untreated animals were compared. The observed carcinogenic effect was based on tumours and lesions found only on the site of application of the test material. Of 210 mice (effective number, 129) serving as the negative controls, three developed skin lesions but no tumours. Of 280 treated animals (effective number, 188) 34 developed different types of tumours and 20 had a uniform type of precancerous skin lesion. Of 34 tumours observed 21 were originated from the skin, 12 from the mammary glands beneath the site of application, and one was a lymphoma. Comparing the negative controls with the treated animals, the overall carcinogenic effect observed was dose-dependent and statistically significant. Excluding the mammary tumours and a lymphoma found beneath the site of treatment, the overall induction of skin tumours was still significant. However, the dose-dependent increase in the number of skin tumours alone was not statistically significant. These results suggest that beech wood dust contains mutagenic and carcinogenic constituent(s).

Animals↗