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    • Urinary hydroxypyrene OHP is a widely used biological marker

    2022-01-17

    Urinary 1-hydroxypyrene (1-OHP) is a widely used biological marker of exposure to PAHs and indicator for internal dose of activated PAHs (Jongeneelen, 1987, Adonis et al., 2003). PAH metabolites may be excreted either as free or as conjugated compounds. When 1-OHP is measured after treating the urine with deconjugating Aurora Kinase Inhibitor III sale (e.g., β-glucuronidase), the sum of conjugated and deconjugated species is quantified, reflecting the total amount of hydroxylate metabolite. Although 1-OHP itself is not a carcinogen, it can be used as a marker for a major activating step in the metabolism of PAHs (Nerurkar et al., 2000). The aim of the present study was to evaluate 1-OHP concentrations in the urine of sugarcane workers, during harvesting (when the sugarcane fields are burnt) and during non-harvesting time, as a biological marker of exposure to PAHs. At the same time, the influence of the genetic polymorphisms CYP1A1, GSTP1, GSTM1 and GSTT1 was also analyzed.
    Materials and methods
    Statistical analysis Urinary 1-OHP levels were log transformed in order to approach normality (tested by the Shapiro–Wilk test). Urinary 1-OHP geometric means (GM) and the respective 95% confidence intervals (95% CI) are reported throughout the analysis. In order to assess group differences in 1-OHP levels, a one-sample (paired) t-test was used for comparing exposed with non-exposed sugarcane workers. One-sample and two-sample t-tests were also used to compare 1-OHP levels in sugarcane workers (exposed and non-exposed) stratified by age (using the median as a cut-off point, 34 years), gender, or CYP1A1 or GST genotypes. Multiple regression analysis was performed to evaluate the relation of 1-OHP levels with possible modulation factors. In this analysis, age, gender and metabolizing genotype were considered potential factors to explain variability in log (1-OHP). A stepwise regression technique was applied, in which independent variables with values of P≤0.25 were included in the final model. The independent variables for genotypes were defined as variants=1 and wild-type=0; CYP1A1⁎1/⁎1=0; CYP1A1⁎1/⁎2A or ⁎2A/⁎2A=1; CYP1A1⁎1/⁎2B or ⁎2B/⁎2B=1; CYP1A1⁎1/⁎4=1; GSTM1 (+/+)=0 or GSTM1 (0/0)=1; GSTT1 (+/+)=0 or GSTT1 (0/0)=1; GSTP1 (Ile/Ile)=0 or GSTP1 (Ile/Val or Val/Val)=1, age and gender (male=1 and female=0). Residual diagnostic was performed for the final models. Additionally, the 1-OHP levels of the non-occupationally exposed group, independent of age and gender, were compared with the two experimental groups by a two-sample (non-paired) t-test. Statistical analysis was performed using STATA, version 8.2.
    Results The concentration of urinary 1-OHP ranged from 0.03 to 2.72 μmol mol creatinine in exposed sugarcane workers, from 0.002 to 2.15 in the non-exposed sugarcane workers and from 0.008 to 0.016 in the non-occupationally exposed subjects. Table 1 shows the geometric means and correspondent 95% CIs for urinary 1-OHP levels, overall and stratified by age and gender. The non-occupationally exposed subjects were not included in tetrad analysis, because almost all ranged in age from 35 to 67 years. In the exposed sugarcane workers, the 1-OHP levels (0.318 μmol mol creatinine) were significantly higher (P<0.0000) than in the non-exposed sugarcane workers (0.035 μmol mol creatinine). The exposed sugarcane workers also had significantly higher 1-OHP levels (P<0.0000) than the non-occupationally exposed subjects (0.041 μmol mol creatinine). Moreover, the 1-OHP levels of the non-exposed sugarcane workers were not significantly different from those of the non-occupationally exposed subjects (P=0.6957). There was a statistically significant difference when the exposed and non-exposed groups were stratified by age and gender (P<0.05). Within the exposed and non-exposed groups, older workers had lower 1-OHP levels than the younger, and this difference was significant in the non-exposed group (P<0.05) (Table 1). The effects of the different genotypes on urinary 1-OHP are shown in Table 2, except for CYP1A1⁎1/⁎4 due to very small sample sizes. No significant difference (P>0.05) was found between 1-OHP levels for any of the polymorphisms.