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Biomedical subjects

A Haugen

Publications and source records attributed to A Haugen.

At least 55 records · Page 3Linked to original sources
PubMed1995

Biological monitoring of polycyclic aromatic hydrocarbon exposure in a highly polluted area of Poland.

Air pollution in Poland and particularly in Silesia is among the worst in Europe. Many coal mines and coke oven plants are located in this area, representing a major source of carcinogenic polycyclic aromatic hydrocarbons (PAHs). We quantitated the PAH exposure level in air samples using personal sampling devices, collected urine samples from the same individuals, and measured 1-hydroxypyrene with high performance liquid chromatography. Samples were collected twice, once in February and once in September. Mean PAH level of samples collected at three different coke oven plants varied from 2.3 micrograms/m3 to 12.3 micrograms/m3; the lowest mean was in September. Mean levels of 0.15 micrograms/m3 (September) and 0.44 micrograms/m3 (February) were noted for the environmentally exposed group. Mean urinary 1-hydroxypyrene varied from 2.45 to 13.48 mumol/mol creatinine at the three coke oven plants. The corresponding variation between the three different environmentally exposed groups in Silesia was 0.41-1.54 mumol/mol creatinine. In the nonindustrialized area, the mean varied from 0.20 to 0.14 mumol/mol creatinine. Seasonal variation was found both at the coke oven plants and in the environmental exposed groups in Silesia. Both PAH levels and 1-hydroxypyrene varied seasonally among coke oven workers and the environmentally exposed group. Our study shows that PAH exposure in the industrialized area of Silesia is high compared to levels in Western Europe. 1-Hydroxypyrene excretion in environmentally exposed individuals in Poland is among the highest in Europe.

Adult↗
PubMed1995

Fertility in mice after prenatal exposure to benzo[a]pyrene and inorganic lead.

Experimental evidence suggests that inorganic lead and benzo[a]pyrene (BaP) suppress the development of primordial oocytes during fetal life. We examined the single and combined effects of prenatal exposure to BaP and moderate doses of lead. The fertility and ovarian morphology of F1 female NMRI mice in four treatment groups (nine mice per group) were investigated: control; lead (F0 given 1 g PbCl2/L in drinking water until mating); BaP (10 mg/kg body weight daily by oral intubation on days 7-16 of F0 pregnancy); and combined lead and BaP. F1 groups exposed prenatally to BaP either alone or in combination with inorganic lead showed markedly reduced fertility with few ovarian follicles compared to controls, whereas the group exposed to lead only had measures comparable to the controls. Mice exposed to both lead and BaP had a significantly longer gestation period (days to litter) compared to mice exposed only to BaP, lead, or controls. There is a nonsignificant indication that the compounds together further reduce number of offspring, number of litters, and litter size. These results suggest that lead and BaP have synergistic effects on impairment of fertility. The possibility of synergism may be of human relevance as inorganic lead and BaP are ubiquitous environmental pollutants.

Animals↗
PubMed1995

Studies of biomarkers in aluminum workers occupationally exposed to polycyclic aromatic hydrocarbons.

Evaluation of biomarkers for genotoxic exposure are important for future use of such biomarkers in cancer prevention. We have studied a group of aluminum plant workers for a period of 2.5 years. The level of polycyclic aromatic hydrocarbons (PAHs) has been monitored at the work place (cathode relining). During the study period, urine and blood were sampled up to seven times from the same workers. Mean level of urinary 1-hydroxypyrene varied from 1.08 to 2.44 mumol/mol creatinine in the exposed groups compared with 0.36 and 0.20 mumol/mol creatinine in the two reference groups. For a group of 14 workers the intraindividual variation of urinary 1-hydroxypyrene was analyzed. The relative standard deviation of the values was < or = 0.50 for half of the workers; the relative standard deviation was calculated for individual values divided by mean of each time point. Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells from exposed and nonexposed workers were measured by both immunoassay and 32P-postlabeling. By 32P-postlabeling mean values of 12.0 adducts/10(8) and 10.8 adducts/10(8) nucleotides were found in a PAH-exposed group and a reference group, respectively. Intraindividual variation of PAH-DNA adducts was also analyzed.

Adult↗
PubMed1994

Different susceptibility to smoking-induced DNA damage among male and female lung cancer patients.

The levels of aromatic/hydrophobic DNA adducts were analyzed in normal lung tissue from 63 lung cancer patients and examined in relation to exposure and genetic factors. Adduct levels were significantly higher in smokers than in nonsmokers, but among smokers the number of cigarettes smoked per day had only low significance for the variation in adduct levels. An inverse correlation was found between years of smoking and DNA adduct levels (r = 0.52, P = 0.001). Thus, patients with high adduct levels generally had shorter duration of smoking and/or lower smoking dose before the clinical onset of the disease, which fits expected behavior of cancer susceptible individuals. The data indicated an excess of individuals with glutathione S-transferase M1 deficiency among male patients with high adduct levels. Among females the DNA adduct levels were higher than in males when adjusted for smoking dose. There was a highly significant difference in the distribution of males and females when smokers were divided into quartile groups according to adducts per pack year (trend test: 2-sided P = 0.005). This may indicate that women are at greater risk of tobacco-induced lung cancer.

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

p53 mutations in lung tumors: relationship to putative susceptibility markers for cancer.

We have screened 108 non-small cell lung tumors for mutational alterations in the p53 gene (exons 5 through 8) using polymerase chain reaction and denaturing gel electrophoresis techniques. Thirty-four cases (32%) had aberrant band migrations. The following DNA-sequencing step confirmed the mutations in all these samples. Seventy-six % of the mutations were found at G:C base pairs. Of all the mutations found, 29% were GC to AT, 29% GC to TA, 15% AT to GC, 12% GC to CG, and 3% AT to CG. The other mutations (12%) were deletions or insertions of one base pair. The frequency of p53 mutations among heavy smokers was higher than in nonsmokers (P = 0.047; odds ratio, 6.75; 95% confidence interval, 0.80-57). We examined p53 mutations in relation to genotypes of GSTmu1 and H-ras1. Our data showed that nearly all heavy smokers with transversion mutations were homozygous for the GSTmu1 null allele (10 of 11). The frequency of such mutations was significantly higher for patients with two null alleles (10 of 25) than for those with at least one allele intact (1 of 18) (P = 0.011; odds ratio, 11.33; 95% confidence interval, 1.29-99.3). This study indicated that rare alleles at the variable number of tandem repeats region flanking the H-ras protooncogene are negatively associated to the presence of p53 mutations in the tumors (P = 0.009).

Alleles↗
PubMed1994

Influence of fatty acids and bovine serum albumin on the growth of human hepatoma and immortalized human kidney epithelial cells.

The protective influence of bovine serum albumin against growth inhibition caused by fatty acids was studied in human hepatoma (HepG2) and immortalized human kidney epithelial (IHKE) cells. In general, growth inhibition by unsaturated fatty acids (0.15 mmol/liter) increased with increasing number of double bonds. For HepG2 cells crude albumin (1 g/100 ml) did not greatly modify growth inhibition by arachidonic, eicosapentaenoic, and docosahexaenoic acid. With oleic, linoleic, and linolenic acids, crude and defatted albumin stimulated cell growth. In contrast, for IHKE cells both albumins counteracted growth inhibition by unsaturated fatty acids to approximately the same extent. When HepG2 cells were cultured in the presence of saturated fatty acids (0.3 mmol/liter), C2, C6, and C8 had no or little inhibitory effect. C10 and C12 inhibited cell growth appreciably, whereas C14, and especially C16, had poor inhibitory effects. Crude albumin counteracted growth inhibition by all these fatty acids. In contrast, defatted albumin had little or no effect (except against C10 and C12), and even increased the growth inhibition by C14 and C16. With unsaturated fatty acids there seemed to be an inverse relationship between cell growth and the concentration of thiobarbituric acid reactive substances (TBARS) in media. Vitamin E abolished growth inhibition (and the increase in TBARS concentration) by unsaturated fatty acids. The complex interaction between fatty acids and albumins calls for great caution when interpreting data on growth effects.

Arachidonic Acid↗
PubMed1994

Biological monitoring of exposure to polycyclic aromatic hydrocarbon in an electrode paste plant.

We have compared several biomarkers for polycyclic aromatic hydrocarbon (PAH) exposure among electrode paste plant workers and workers not occupationally exposed to PAH. The PAH exposure was quantitated from samples collected with person-attached sampling devices. The mean particulate PAH exposure level in the plant was 14.4 micrograms/m3. The level of pyrene was significantly correlated with both PAH level and the level of selected carcinogenic PAHs in this type of exposure. The mean concentration of the biomarker 1-hydroxypyrene in the PAH exposed workers' urine was 6.98 mumol of 1-hydroxypyrene per mole of creatinine compared with 0.08 and 0.14 mumol of 1-hydroxypyrene per mole of creatinine in the two reference groups. PAH-DNA adducts were measured in DNA from white blood cells by the ultrasensitive enzyme radioimmunoassay (USERIA) and the 32P-postlabeling technique. Only urinary 1-hydroxypyrene was significantly increased in the PAH-exposed group.

Adult↗
PubMed1994

Nickel-induced alterations in human renal epithelial cells.

Cellular progression to malignancy appears to require a number of distinct steps in which genetic damage in key regulatory genes accumulates. Immortalization, or escape from senescence, is considered to be one of the first phenotypic changes. Ni2+ treatment of normal human kidney epithelial (NHKE) cells in vitro resulted in immortalization of the cells IHKE cells). The combined action of Ni2+ and v-Ha-ras oncogene fully transformed the cells to tumorigenicity in athymic nude mice. Sequence analysis of DNA from IHKE cells revealed point mutation in the p53 gene at codon 238 with T-->C transition. These findings suggest that Ni-induced mutation in the p53 gene can be involved in the immortalization of the NHKE cells. The results also show that changes in the responses to EGF and TGF beta and in the expression of their receptors occur during malignant progression in vitro.

Carcinogens, Environmental↗
PubMed1993

Microsatellite instability is associated with tumors that characterize the hereditary non-polyposis colorectal carcinoma syndrome.

Microsatellite instability implying multiple replication errors (RER+ phenotype) characterizes a proportion of colorectal carcinomas, particularly those from patients with the hereditary non-polyposis colorectal carcinoma syndrome. We studied the incidence of microsatellite instability in more than 500 sporadic tumors representing 6 different types of cancer. Apart from colorectal carcinoma [see the paper by Lothe et al. (Cancer Res., 53:5849-5852, 1993)] the RER+ phenotype was found in 18% (6 of 33) of gastric carcinomas and 22% (4 of 18) of endometrial carcinomas. In contrast, no evidence of this abnormality was detected in cancers of the lung (N = 85), breast (N = 84), and testis (N = 86). Importantly, the first three cancers, as opposed to the latter three, are characteristic of the hereditary non-polyposis colorectal carcinoma syndrome. These findings suggest that the cancers belonging to the hereditary non-polyposis colorectal carcinoma tumor spectrum may have essential pathogenetic steps in common, including a tendency to multiple replication errors.

Chromosome Deletion↗
PubMed1993

Karyotypic changes in the preclinical and subsequent stages of malignant mesothelioma: a case report.

The karyotypic evolution was evaluated in cells from recurring pleural effusions in a patient previously exposed to asbestos. Pleural malignant mesothelioma (MM) was diagnosed 4 years after the first cytogenetic examination. The primary cytogenetic changes consisted of loss of chromosomes 1p,14,21, Y, both 22, and derivative chromosomes involving 1, 2, and 14. The modal chromosome number was 44. Sixty-seven percent of the cells had a normal karyotype. After 4 years of spontaneous remission, only 6% of the cells had a normal karyotype, 42% had the same karyotypic changes as found previously, whereas 52% had additional derivative chromosomes involving chromosomes 1, 3, 5, 7, 8, and 12, trisomy 7, 7p, and 11, and partial or whole monosomy 3, 8, and 9. The chromosomal changes are in agreement with the main findings in previous reports. The karyotype remained quite stable for 7 months in vitro. After 23 months in culture, all the cells were near-triploid. Cells established in culture were cytokeratin positive. All derivative and marker chromosomes identified in the cultured cells had previously been observed in direct preparations from the pleural effusions. We conclude that chromosomes 1, 14, 21, and 22 may be involved in the preclinical stage of development of asbestos-induced mesothelioma, whereas the later chromosomal changes may be related to progression of the tumor.

Aged↗
PubMed1993

Rare Ha-ras1 alleles and predisposition to testicular cancer.

We have examined the restriction-fragment-length polymorphism (RFLP) of the VNTR region flanking the Ha-ras1 gene in genomic DNA from 348 testicular cancer patients and 343 healthy controls. When DNA samples were digested with MspI/HpaII, Southern blot analysis revealed 24 and 15 different alleles in the cancer and the control group respectively. The frequency of rare alleles among cases was significantly higher than in controls. Patients with bilateral cancer and patients with unilateral cancer below 20 years had significantly higher incidence of rare alleles than patients with unilateral cancer older than 20 years.

Adult↗
PubMed1993

Effect modification by inorganic lead in the dominant lethal assay.

Experimental evidence suggests that inorganic lead may modify mutagenic events. We examined the modifying effect of lead on mutagenic events in late spermatogenesis in the dominant lethal assay. Twelve NMRI male mice were given lead chloride in the drinking water and 12 male mice received tap water without lead chloride. Cyclophosphamide (120 mg/kg b.w., i.p.) was given to six males in the lead treatment group and six males in the tap water group 1 week before mating. This resulted in four treatment groups: control, lead, cyclophosphamide, and lead plus cyclophosphamide. Cyclophosphamide given to the males (with or without lead treatment) reduced the numbers of live implants in mated females. The most prominent effect of cyclophosphamide was an increase of resorbed implants. Females mated to lead exposed male mice showed a nonsignificantly lower frequency of resorptions compared to controls. The results give no support to the hypothesis that inorganic lead may influence the mutagenicity of cyclophosphamide in the dominant lethal test.

Animals↗
PubMed1993

Determination of polycyclic aromatic hydrocarbons in urine from coke-oven workers with a radioimmunoassay.

Considerable amounts of polycyclic aromatic hydrocarbons (PAH) are present in the workplace. In order to obtain a better understanding of the occupational hazards connected with PAH exposure various biomonitoring methods need to be applied. The level of PAH in urine collected from coke-oven workers has been measured by a recently developed radioimmunoassay. A significant correlation between estimated exposure levels for PAH and urinary levels of PAH was observed. During the winter period the control group was found to have an average concentration of 0.44 ng PAH/mmol creatinine, whereas the low, medium and high exposure groups contained 0.44, 0.71 and 0.85 ng PAH/mmol creatinine respectively. The urinary PAH level in the samples collected during the summer period was higher, i.e. 0.81, 0.94 and 1.10 ng PAH/mmol creatinine, for the low, medium and high exposure groups. Furthermore, a correlation was also observed between smoking and levels of urinary PAH. We conclude that this radioimmunoassay may be suitable as a simple and sensitive routine assay for monitoring individuals exposed to PAH.

Biomarkers↗
PubMed1992

Detection of polycyclic aromatic hydrocarbon-DNA adducts in white blood cells from coke oven workers: correlation with job categories.

Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were quantitatively determined by ultrasensitive radioimmunoassay (USERIA) and 32P postlabeling in 128 DNA samples from WBCs of 68 coke oven workers and a local control group of 13 workers. Forty-four samples had a detectable adduct level by USERIA, with a mean of 0.390 fmol adducts/micrograms DNA (12.9 adducts/10(8) nucleotides) in the exposed group compared to a mean of 0.316 fmol adducts/micrograms DNA (10.4 adducts/10(8) nucleotides) in the control group. The mean adduct level with 32P postlabeling was 0.05 fmol/micrograms DNA (1.67 adducts/10(8) nucleotides) for the exposed group and 0.046 fmol/microgram DNA (1.54 adducts/10(8) nucleotides for the control group. Based on job description the workers were divided in 4 groups: control, low-, medium-, and high-exposure group. Both methods produced a positive correlation coefficient between estimated exposure and PAH-DNA adduct levels. The significance levels determined with Kendall rank correlation were P = 0.0145 for USERIA and P = 0.0594 for 32P postlabeling. Adduct levels determined by 32P postlabeling showed a correlation with tobacco smoking in the control group. No significant correlation between PAH-DNA adduct levels measured by USERIA and 32P postlabeling was found. These results show that these methods recognize different parts of the complex exposures in a coke oven plant.

Coke↗
PubMed1992

Altered p53 gene structure and expression in human epithelial cells after exposure to nickel.

The carcinogenicity of certain nickel compounds is well known. We have previously shown that human kidney epithelial cells were immortalized by treatment with Ni(II) and in cooperation with the v-Ha-ras oncogene transformed the cells to acquire tumorigenicity in athymic nude mice. Immunocytochemistry and sequence analysis of DNA from the nickel-immortalized cells revealed abnormal p53 expression and a T----C transition mutation in codon 238. These data are consistent with the hypothesis that Ni(II)-induced mutation in the p53 gene can be involved in the escape from senescence of kidney epithelial cells.

Cell Line, Transformed↗
PubMed1992

Allele diversity of the H-ras-1 variable number of tandem repeats in Norwegian lung cancer patients.

We have examined restriction fragment length polymorphisms of the H-ras-1 gene in germ-line DNA from 214 lung cancer patients and 309 unaffected controls. When DNA samples were digested with MspI/HpaII, Southern blot analysis revealed at least 22 different alleles, grouped according to their frequencies as common, intermediate, and rare. The frequency of rare alleles in lung cancer patients (16/428) is significantly different (p = 0.002) from that in the control group (5/618). Individuals with rare alleles were found to be at 4.7-fold greater risk of lung cancer than those with no rare alleles.

Alleles↗
PubMed1991

Levels of environmental pollutants in male and female flounder (Platichthys flesus L.) and cod (Gadus morhua L.) caught during the year 1988 near or in the waterway of Glomma, the largest river of Norway. I. Polychlorinated biphenyls.

Levels of polychlorinated biphenyls, PCBs, in liver samples of 111 and 121 flounder (Platichthys flesus L.) and cod (Gadus morhua L.), respectively, were determined gas chromatographically by quantification of 9 individual PCB congeners. The congeners were 28, 52, 101, 118, 153, 138, 180, 170, and 209 (IUPAC numbering system, Ballschmiter and Zell 1980). The fish were caught during 1988 at 5 different stations near or in the Glomma estuary, in the Hvaler archipelago, Norway. The mean level of the sum of the congeners, 1,050 ng/g, found in cod was 3 times higher than the corresponding level found in flounder (361 ng/g). The influences on the variation in PCB levels of sex, season, and distance from the Glomma outlet and waterway were investigated using 1-, 2-, and 3-way ANOVA. The main effects of these factors as well as their possible interactions were considered. An expected decreasing PCB pollution gradient from the mouth of Glomma was found for cod, while PCB levels in flounder seemed to be less dependent on sampling site. However, the sexes in both fish species exhibited a different pattern in their PCB levels. The PCB levels in female cod were significantly affected by the season of sampling, with PCB levels in September/October significantly greater than the corresponding levels in June and November/December. No such effect was found for male cod. In flounder, a significant station effect on the PCB levels was found for females only, and a decreasing PCB pollution gradient was found to be significant. The interactions between the three factors station, season, and sex were different in the two species.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗