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Sökning: WFRF:(Albin Maria) > Jönsson Bo A

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  • Hedmer, Maria, et al. (författare)
  • Validation of urinary excretion of cyclophosphamide as a biomarker of exposure by studying its renal clearance at high and low plasma concentrations in cancer patients
  • 2008
  • Ingår i: International archives of occupational and environmental health. - Springer Berlin / Heidelberg. - 0340-0131. ; 81:3, s. 285-293
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Cyclophosphamide (CP) is an alkylating agent classified as a human carcinogen. Health care workers handling this drug may be exposed during, e.g., preparation or administration. Cyclophosphamide is readily absorbed by inhalation and by dermal uptake. A biomarker, CP in urine, has frequently been used to assess the occupational exposure to CP, but has not been fully validated. The aim of this study was to investigate if the proportion of the CP dose that is excreted in urine (renal clearance) is constant over different plasma drug concentrations and other pharmacokinetic parameters, e.g., urine flow. METHODS: Pharmacokinetics of CP were studied in 16 breast cancer patients that were treated with postoperative adjuvant chemotherapy including CP. Plasma and urine from the patients were collected at different occasions up to 12 days after the dose. Urine was collected during 4-h periods and blood was sampled at the end of each period. Analysis of CP was performed by liquid chromatography tandem mass spectrometry. The limit of detection for CP in urine and plasma was 0.01 and 0.02 ng/ml, respectively. The precisions of the developed methods were determined to </=8%. RESULTS: The administered doses of CP in absolute amounts ranged between 800 and 2,240 mg. Mean renal clearance of CP was 8.6 (confidence interval 6.5-10.7) ml/min and was not significantly dependent of the plasma drug concentration. However, a significant correlation between renal clearance and urine flow was observed. There was a large inter-individual variation in the plasma and urine concentrations even when the same doses were given. CONCLUSIONS: Cyclophosphamide in urine can be continued to be used as a biomarker to monitor occupational exposure to CP, however the inter-individual variability of excretion of CP in urine, and its dependency on urine flow must be taken into consideration in future applications.
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  • Li, Huiqi, et al. (författare)
  • N-nitrosamines are associated with shorter telomere length.
  • 2011
  • Ingår i: Scandinavian journal of work, environment & health. - 1795-990X. ; 37, s. 316-324
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Telomeres are critical to maintain the integrity of the chromosomes, and telomere abnormalities are important features of carcinogenesis. Telomere length differs among individuals due to genetic and environmental factors. Aiming to examine the relationship between DNA-damaging agents and average telomere length in peripheral blood, we conducted a cross-sectional study among 157 workers working in the rubber industry in Sweden. METHODS: N-nitrosamines were measured in air by personal sampling on Thermosorb/N tubes and analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS) for 60 individuals. Based on a similar working situation, the exposure was estimated for all workers. Polycyclic aromatic hydrocarbons (PAH) were measured as the metabolite 1-hydroxypyrene (1-HP) in urine by LC. Carbon disulphide (CS2) was measured as the metabolite 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine by LC/MS/MS. Toluidines (orto-, meta-, and para-) were measured in urine by gas chromatography (GC)/MS. The average telomere length in peripheral blood was determined by quantitative polymerase chain reaction (PCR). RESULTS: There was a reduction in telomere length with increasing exposure to N-nitrosamines in air measured (N=60) N-nitrosamines β-coefficient= -10, (95% confidence interval 95% CI -19- -1.2) P=0.026; estimated (N=157) N-nitrosamines β-coefficient = -5.3, (95% CI -9.5- -0.97) P=0.016. Also, there were negative associations between para-toluidine β-coefficient= -0.031 (95% CI -0.055- -0.0063) P=0.014, as well as age β-coefficient= -0.005 (95% CI -0.007- -0.002) P=0.001 and telomere length. There were no strong associations between other exposures and telomere length nor did smoking modify the effect. CONCLUSION: N-nitrosamines exposure may lead to telomere shortening.
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