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Biomedical subjects

B Holmberg

Publications and source records attributed to B Holmberg.

At least 19 recordsLinked to original sources

The effects of long-term oral administration of ethanol on Sprague-Dawley rats--a condensed report.

For a period of 2 years Sprague-Dawley rats received 3% and 1% ethyl alcohol or an equicaloric amount of glucose in a semisynthetic liquid diet. Thereafter the tumour incidence was recorded. For male rats no neoplastic lesions were observed to be related to ethanol exposure. For females, when individual group comparisons were made, an increase in mammary gland tumours was seen for females receiving the low ethanol containing diet. In some tumour frequency comparisons the opposite, namely a decrease in the rate of incidence, was obtained. The overall information seems to indicate the absence of a carcinogenic activity of ethyl alcohol per se after long-term oral administration. Liver and bile duct injury was seen among males. Inflammatory reactions were seen among males in pancreas and for females in the clitoral gland. Hyperplasia was observed in the thyroid gland in both sexes and in the adrenal glands among females. Peripheral nerve degeneration was common in both sexes.

Animals

Exposure to extremely low frequency electromagnetic fields and the risk of malignant diseases--an evaluation of epidemiological and experimental findings.

Epidemiological and experimental studies concerning extremely low frequency electromagnetic field exposure and malignant diseases published up to 1 July 1994 were evaluated to assess the possible carcinogenicity of electromagnetic fields and the scientific basis for environmental and occupational standard setting. We concluded that there are possible associations between (i) an increased risk of leukaemia in children and the existence of, or distance to, power lines in the vicinity of their residence, (ii) an increased risk of chronic lymphatic leukaemia and occupational exposure to low frequency electromagnetic fields and (iii) an increased risk of breast cancer, malignant melanoma of the skin, nervous system tumours, non-Hodgkin lymphoma, acute lymphatic leukaemia or acute myeloid leukaemia and certain occupations. There is no scientific basis for occupational or environmental standard setting for low frequency electric or magnetic fields.

Adult

Magnetic fields and cancer: animal and cellular evidence--an overview.

A few animal studies on the possible carcinogenic effect of magnetic fields have been published. They have been designed to reveal a possible tumor promotion obtained by applying continuous or pulsed alternating fields at flux densities varying between 0.5 microT and 30 mT on mice or rats initiated with different initiators. One study with 2 mT applied on DMBA-initiated mice may suggest a copromotive effect together with the promoter TPA. Another study on rats suggests an inhibitory effect by a magnetic field on rat liver foci formation, induced with DENA. Cell studies show that magnetic fields at some frequencies, amplitudes, and wave forms interact with biological systems. Thus effects have been seen, e.g., on enzymes related to growth regulation, on calcium balance in the cell, on gene expression, and on pineal metabolism and its excretion of the oncostatic melatonin. Cellular and physiologic studies thus suggest effects that may be related to cell multiplication and tumor promotion.

Animals

Intermittent 50 Hz magnetic field and skin tumor promotion in SENCAR mice.

A number of epidemiological studies have indicated association between exposure to extremely low frequency electromagnetic fields and a variety of cancers, including leukaemia and brain tumours among residentially exposed children and among occupationally exposed adults. In order to test if intermittent magnetic fields (MF) act as a tumour promoter, a long-term skin carcinogenicity study of 50 Hz sinusoidal MF with flux densities of 50 muT and 0.5 mT, continuous as well as with an intermittence of 15 s on/off, was performed. Female SENCAR mice were divided into eight groups of 50 animals in each and treated according to an initiation- promotion scheme. 7,12-dimethylbenz[a] anthracene (DMBA) in acetone was applied to the dorsal skin at a subcarcinogenic dose, as an initiator and exposure to MF was performed for 19-21 h/day during 104 weeks starting 1 week after the initiator treatment. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was used as a positive control for skin tumour promoting activity. Two animals from each group were assigned for skin hyperplasia analysis at 2, 6, 12, 18 and 21 months. The animals were observed daily. The appearance of skin lesions and neoplasms were carefully followed and histopathological diagnosis was made for all neoplasms present at death. The experiment was terminated after 105 weeks. DMBA-treatment alone yielded altogether two skin tumours in two tumour-bearing animals and the animals exposed to acetone alone had one skin tumour. The animals exposed to continuous fields showed no skin tumour. Five animals exposed to 0.5 mT on/off had a total of 13 skin tumours and in the group exposed to 50 microT on/off four animals had a total of four skin tumours. The on/off exposed groups differed significantly from the continuously exposed groups (P = 0.014) but the difference between the on/off exposure groups and the DMBA group was not statistically significant when tumour-bearing animals and cumulated skin tumours were compared. There was a statistically significant dose trend (P = 0.045) with flux density and Tesla-h for intermittent MF exposure for cumulated skin tumours per tumour-bearing animals. The epithelial thickness of DMBA + MF-treated animals was of the same magnitude as for DMBA-treated animals indicating that, in the case of a promoting effect being present, another mechanism than one involving sustained hyperplasia may be involved.

9,10-Dimethyl-1,2-benzanthracene

Mortality and cancer incidence among PVC-processing workers in Sweden.

The mortality pattern and the cancer incidence were investigated among 717 men who had been employed for at least 3 months during 1964-1974 in three Swedish PVC-processing plants. The mortality was followed 1964-1986 and the cancer incidence 1964-1984. Expected figures were calculated from Swedish national rates. Among Swedish citizens, the observed mortality and cancer incidence was close to the expected in most diagnoses. Among immigrants, mostly from Finland, there was a marked excess of circulatory deaths. This finding was probably due to the higher incidence of coronary mortality in Finland compared to Sweden. In the whole cohort, five cases of malignant melanoma had occurred as compared to 1.5 expected (SMR = 3.4, 95% confidence limit 1.1-7.9). This may be due to chance but merits further investigation since an increased incidence of malignant melanoma has previously been found among Norwegian PVC-manufacturing workers.

Chemical Industry

Rat liver foci study on coexposure with 50 Hz magnetic fields and known carcinogens.

A study was performed to investigate possible interactions by magnetic fields (MF) with the processes of initiation and promotion of chemically induced preneoplastic lesions in rat liver. Male Sprague-Dawley rats were subjected to a 70% partial hepatectomy followed after 24 h by i.p. injection of diethylnitrosamine (DENA) as a tumour initiator. Starting one week after the DENA-treatment phenobarbital (PB) was given to promote growth of enzymatically altered foci of liver cells. MF was applied immediately after the partial hepatectomy and continued until sacrifice after 12 weeks of PB exposure. Homogenous horizontal AC magnetic fields with a frequency of 50 Hz and flux densities of 0.5 mu T or 0.5 mT were used. The rats coexposed with MF and DENA plus PB did not gain weight as much as the rats exposed to the chemical agents only. The MF-exposure also resulted in a slight reduction in size and numbers of the focal lesions. The results suggest an interaction of MF with the processes of chemical carcinogenesis either as a result of stress or depending on effects on the proliferation of preneoplastic cells.

Animals

Single-dose L-dopa response in early Parkinson's disease: measurements with optoelectronic recording technique.

Twenty-five patients with suspected Parkinson's disease were submitted to optoelectronic movement analysis with the Posturo-Locomotor-Manual (PLM) test before and 60 min after a single dose of L-Dopa. They were then examined clinically for diagnosis. Two patients were excluded due to L-Dopa intolerance. Seventeen of the remaining patients were classified as having Parkinson's disease. The movement time (MT) in the PLM test was increased for all these patients, and they improved their performance after L-Dopa. The degree of improvement was roughly proportional to the pretreatment augmentation of MT in comparison to healthy subjects of the same age. The PLM phase analysis showed a specific disability profile for each individual. Six patients were given diagnoses other than PD. Some improvement was found in one patient with suspected olivopontocerebellar atrophy and one patient with multiple brain injury. Two patients with progressive supranuclear palsy, one with suspected striatonigral degeneration, and one with functional disturbance deteriorated after L-Dopa. In conclusion, truly objective and fully reproducible evaluation of the motor performance before and after a single L-Dopa dose is easily accomplished with computer-assisted modern optoelectronic recording equipment. The technique is a valuable tool for the quantitative measurement of treatment effects and contributes to the differential diagnosis.

Adult

A rat liver foci promotion study with 50-Hz magnetic fields.

To investigate the possible tumor-promoting effect of magnetic fields (MF), we have performed two liver foci bioassays in rats which were exposed to MF at four flux density levels (0.5 microT, 5 microT, 0.05 mT, and 0.5 mT). The MF were generated in exposure equipment consisting of copper coils surrounding racks with animal cages and giving homogenous horizontal 50-Hz magnetic fields. Rats previously submitted to partial hepatectomy and diethylnitrosamine treatment were exposed to MF for 12 weeks. Exposed and control rats were kept in separate rooms. As a positive control phenobarbital (PB) was administered for 12 weeks. The number, area, and volume of foci expressing gamma-glutamyl transpeptidase (GGT) and glutathione S-transferase (GST-p) were evaluated. The body weight gains and relative liver weights of MF-exposed rats were not different as compared to control rats. There was a slight increase in GGT-staining foci, but not in GST-p-staining foci, in the groups exposed to flux densities of 0.5 microT and 0.05 mT compared to the control group in the first experiment. The number of both GGT- and GST-p-staining foci in the livers of all MF-exposed groups were, however, within the control range when the results of the two experiments were considered together.

Animals

Lymphoma development among mice exposed to X-rays and pulsed magnetic fields.

CBA mice were exposed to a total of 5.24 Gy X-rays (260 kV, 11 mA, 0.45 Gy/min), divided into four exposures, and to saw-tooth 15 microT (peak to peak) pulsed vertical 200 kHz magnetic fields for their life-time. In parallel, series with magnetic fields only or non-exposed animals were run. The animals were observed for their life-time. The frequency of lymphomas was 65.7% in the X-ray group and 71.4% in the groups exposed to both X-ray and magnetic field. Of the non-exposed control animals, and of the animals exposed to magnetic fields only 6.4 and 5.7% had lymphomas, respectively. There were no statistically significant differences between the magnetic field series and the corresponding controls for lymphomas. Blood cell counts and haemoglobin data did not show differences between the X-irradiated, and X-ray and magnetic field-exposed groups. Mononuclear cells and total leukocytes were elevated for pulsed magnetic fields-exposed animals compared with the non-exposed controls. This difference was due to two animals with extreme values. In the pulsed magnetic fields treated group there was a statistically significant increase of the carcass weight compared with the non-treated control group.

Animals

A study on skin tumour formation in mice with 50 Hz magnetic field exposure.

In order to test the possibility that magnetic fields (MF) act as a tumour promoter, a long-term skin carcinogenicity study of 50 Hz sinusoidal MF with flux densities of 50 microT and 0.5 mT was performed in female NMRI mice. 7,12-dimethylbenz[a]anthracene (DMBA) in acetone was applied to the dorsal skin, as an initiator, and exposure to MF was performed for 19 (weekdays) or 21 h/day (weekends and holidays) for 103 weeks starting one week after the initiator treatment. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was used as a positive control for skin tumour promoting activity. MF was also evaluated for complete carcinogenic action in groups of mice that were treated with acetone only. Six animals from each group were taken for skin hyperplasia analysis and were killed after 9, 26 and 52 weeks. The appearance of skin lesions were carefully followed and histopathological diagnosis was made for all neoplasms present at death. The statistical analyses on occurrence of skin tumour bearing animals and cumulated skin tumours, with corrections for survival did not reveal a difference between the controls and the MF exposed groups. The epithelial thickness of DMBA + MF-treated animals was of the same magnitude as for DMBA-treated animals. Leukaemia was a little more frequent among animals exposed to 0.5 mT MF compared to the control animals. However this difference was not statistically significant.

9,10-Dimethyl-1,2-benzanthracene

New Swedish occupational standards for some organic solvents.

In 1987, the Swedish government requested a unique investigation of the consequences of a 50% reduction of permissible exposure levels (PEL) for organic solvents. As a result, 29 solvents were investigated and for 25 of them a reduction--if not to 50%--was suggested. For 13 of the solvents, there existed scientific arguments for a reduction of the PEL. For 12 solvents, no specific biomedical information was available. Presumed interactions between solvents may have influenced the decisions, but technological/economic feasibility criteria may also have been used by the regulators. This suggests that the use of technological/economic feasibility criteria can give lower PELs than health criteria. This is within the intentions of the Swedish Work Environment Act.

Acetates

Occupational implications of the chlorofluorocarbon ban in Sweden.

Limitations on the use of full halogenated chlorofluorocarbons (CFCs) may create occupational environmental problems. These are currently largely unknown, because the toxicology of most CFC substitutes is unknown. Therefore, toxicity testing of CFC substitutes is necessary, and this can best be done before their use commences. Destruction of CFC and materials containing CFC could generate new chemical compounds, especially during incineration. In addition, problems with higher noise and vibration levels may occur when CFC substitutes are employed, and we should keep in mind that occupational environment problems could also develop when new routines are introduced for transporting, storing, and handling new materials.

Humans

CSF and urine biogenic amine metabolites in Rett syndrome.

The metabolites of dopamine (homovanillic acid-HVA), noradrenaline (4-hydroxy-3-methoxy-phenylglycol-HMPG), and serotonin (5-hydroxyindoleacetic acid-5-HIAA) were measured in cerebrospinal fluid (CSF) from 38 patients and urine from 36 patients with typical Rett syndrome (RS) and compared with controls of similar age. CSF metabolite concentrations were the same in the patients and controls. Urinary metabolites expressed per mol creatinine were significantly higher in older RS patients. This difference is partly explained by lower urinary creatinine levels in older RS patients, due to their known reduction in muscle mass. Alterations in CSF or urine biogenic amine metabolite concentrations do not appear to represent the primary abnormality in RS, and their measurement cannot be regarded as a reliable means of diagnosis.

Adolescent