Genetic damage of operating and recovery room personnel occupationally exposed to waste anaesthetic gases.

Occupational exposure to the waste anaesthetic gases (WAGs) is a crucial problem for healthcare personnel. Cancer is among the potential long-term adverse effects of WAGs. The present occupational molecular epidemiology study was conducted in healthcare personnel (anaesthetists, nurses and technicians; n = 46), working in operating rooms (ORs; n = 34) and recovery units (RUs; n = 12) of the same hospital, to assess the genotoxicity risk of WAGs exposure. Twenty-one healthy available hospital staff allocated to other wards, without the history of working in ORs and RUs were the control group. A micronucleus test was carried out for peripheral blood lymphocytes (PBLs) and buccal epithelial cells (BECs). Exposure to the anaesthetics was assessed with sevoflurane concentrations and inorganic fluoride levels in post-shift urine samples of the healthcare staff. As an exposure marker, sevoflurane concentrations in ORs and RUs were measured using passive samplers. The micronuclei frequencies were increased in both PBLs (approximately two times) and BECs (approximately three times) of the healthcare personnel. Urinary sevoflurane concentrations exceeded the biological equivalent level in 23 personnel. Air sevoflurane levels in the breathing zone in three ORs and one RU did not exceed the established occupational exposure limits. Both in surrogate tissue (PBLs) and in target tissue (BECs) of the personnel of RUs and ORs of the same hospital, the genotoxicity risk was evident and similar. Originality of this study, in addition to the WAGs exposure confirmation of the healthcare personnel, was the involvement of the RU personnel for the genotoxicity assessment, which was the first time in the scientific literature.

Effects of vitamin C and N-acetylcysteine against cyclophosphamide-induced genotoxicity in exfoliated bladder cells of mice in vivo.

PURPOSE: To investigate the effects of vitamin C and N-acetylcysteine (NAC) against cyclophosphamide (CP) -induced genotoxic damage in exfoliated bladder cells of mice by micronucleus (MN) assay. METHODS: For each experimental step, 6-8 Swiss albino balb/c male mice were used. CP was used as positive control. Vitamin C (10, 30 and 60 mg/kg) and CP (51.6 mg/kg) were administered intraperitoneally to the experimental animals. Vitamin C was administered twice, one dose 24 h prior to the CP administration and the second dose simultaneously with the CP. NAC (200, 400 and 800 mg/kg) was administered by gavage for 7 consecutive days before the injection of CP. Distilled water and normal saline as negative controls I and II were used, respectively. Ten days after CP treatment, the mice were sacrificed and bladders were isolated and cut, and exfoliated cells were scraped from the bladder walls. Air-dried smears were stained by Feulgen reaction. MN frequencies were scored in 1000 epithelial cells per animal and defined as MN per thousand (per thousand). RESULTS: Three doses of vitamin C (10, 30 and 60 mg/ kg) showed a significant inhibitory effect on MN frequencies in mouse bladder cells when compared with those of positive control group (p <0.05). Dose-dependent inhibitory effect of vitamin C was observed only between the doses of 10 and 60 mg/kg (p <0.05). Histopathological changes that depended on CP- induced inflammatory infiltration and haemorrhage in mucosa propria were not observed in all 3 vitamin C doses. Three doses of NAC (200, 400 and 800 mg/kg) inhibited the CP-induced genotoxicity (p <0.05), however, the antigenotoxic effect of NAC was not dose-dependent. Histopathological changes that depended on CP-induced inflammatory infiltration and haemorrhage in mucosa propria were not observed in 200 and 400 mg/kg NAC dosage. The extent of desquamation in bladder was similar in all 3 doses of NAC when compared with the positive control group. CONCLUSION: Our study indicated that vitamin C and NAC reduced the CP-induced MN frequencies in target (bladder) cells of mice by 41-71% in all cases. The modifying effects of vitamin C and NAC against CP-induced genotoxic damage may be due to their antioxidant, nucleophilic properties and to the ability to act as precursors of glutathione.

Assessment of genotoxic damage in nurses occupationally exposed to antineoplastics by the analysis of chromosomal aberrations.

To estimate the genotoxic risk of occupational exposure to antineoplastic drugs, chromosomal aberration (CAs) frequencies in peripheral lymphocytes were determined for 20 nurses handling antineoplastics and 18 referents matched for age and sex. Urinary cyclophosphamide (CP) excretion rates, which are used as a marker for drug handling, were also measured on these nurses. We have observed significant frequencies of CAs (about 2.5-fold increase) including chromatid breaks, gaps, and acentric fragments for nurses handling antineoplastics as compared to control subjects (p < 0.05, p < 0.01, excluding and including gaps, respectively). The mean value of CP excretion rate for 12 nurses was 1.63 microg/24 h, suggesting that when the nurses handled CP (and other antineoplastic drugs) this particular compound was absorbed. Our study has shown that increased genetic damage was evident in nurses, at population level, due to occupational exposure to antineoplastics. Until the effects of handling antineoplastics from low-level exposure are known, it will be important to keep the exposure to a minimum.

Micronuclei frequencies in exfoliated nasal mucosa cells from pathology and anatomy laboratory workers exposed to formaldehyde.

Formaldehyde (FA) is a widely used industrial chemical. Sufficient evidence exists to consider FA as an animal carcinogen. A possible causal role for FA may be considered likely for cancer of the nasopharynx and the nasal cavities in humans. The frequency of micronuclei (MN) in cells of the nasal mucosa was evaluated for 23 individuals in pathology and anatomy laboratories exposed to FA. Twenty-five healthy subjects were selected from the university and hospital staff as a control group. The measured air concentrations of FA in the breathing zone of the laboratory workers were between 2 and 4 ppm. The mean +/- SD values of nasal mucosa MN (per 1000) frequency from exposed and controls were 1.01 +/- 0.62 and 0.61 +/- 0.27, respectively (p < 0.01). Effect of smoking, age, sex and duration of exposure on the genotoxicity parameters analyzed were also evaluated. Our data suggest that low level exposure to FA is associated with cytogenetic changes in epithelial cells of the nasal region and that nasal mucosa cells exposed through respiration is an important target of FA-induced genotoxic effects.

Monitoring of genotoxic damage in smokeless tobacco ((Maras powder) consumers using micronucleated exfoliated oral cells.

Maras powder is a kind of smokeless tobacco used in the south-eastern region of Turkey. The present study was carried out to assess possible DNA damage in exfoliated oral cells of Maras powder users by analysing the frequencies of micronuclei (MN), which is a simple and reliable biomarker for genotoxic damage and to screen for the detection of site-specific differences in the frequencies of MN. The mean (±SD) MN frequency in the inner lip mucosa site was 1.27(±0.55) % for Maras powder users and 0.88(±0.47) % for non-smoking control subjects (p < 0.05) and 0.82(±0.40) % for the buccal site of Maras powder users (p < 0.01). There was no significant site-specific difference between the inner lip site and the buccal mucosa site 0.73(±0.43) % in the MN frequency of non-smoking control subjects (p > 0.05). There was no significant effect of daily consumption of Maras powder, and duration of usage on MN frequencies. The present study suggests that the oral use of smokeless tobacco represents a genotoxic hazard and also that use of MN from a single site may be misleading as a marker of genotoxic exposure. Habitual use of Maras powder should be taken into account and could be considered unsafe.

Effects of occupational chronic co-exposure to n-hexane, toluen, and methyl ethyl ketone on NK cell activity and some immunoregulatory cytokine levels in shoe workers.

1. To evaluate the effects of occupational long-term co-exposure to n-hexane, toluen, and methyl ethyl ketone (MEK) on NK cell activity and serum IL-2, gamma-IFN levels, we studied a group of workers employed in a shoe factory where the jobs include use of glues and adhesives containing mainly n-hexane, and at low concentrations, toluen and MEK. 2. No differences were found in these parameters even in those workers with 3.3-fold higher mean levels of urine, 2,5-Hxdn and approximately twofold higher mean levels of urine hippuric acid as compared to controls. 3. We conclude that chronic co-exposure to n-hexane, toluen, and MEK at these levels is not associated with an impairment on either NK cell activity or serum IL-2 and gamma-IFN levels.

Investigation of some immunological functions in a group of asphalt workers exposed to polycyclic aromatic hydrocarbons.

To investigate the effects of polycyclic aromatic hydrocarbons (PAHs) on the human immune system, analyses were performed on T-cell subsets (CD4+, CD8+), B-cells (CD19+), serum immunoglobulin levels (IgG, IgM, IgA) and white blood cell percentages of 16 male workers who were employed in road paving operations and compared to 12 unexposed male controls. PAH exposure was assessed using urinary 1-hydroxy-pyrene (1-OHP) levels and was found to be significantly higher in workers than in the controls. While the CD4+ cell percentage and the CD4+/CD8+ ratio were significantly higher in the PAH-exposed group, the percentages of CD8+ and CD19+ cells were unchanged. There was also a significant enhancement in serum IgG levels and the percentage of monocytes in the workers compared to the control group. These data suggest that chronic exposure to PAHs may affect some immune functions in humans.

The micronucleus assay in exfoliated buccal cells: application to occupational exposure to polycyclic aromatic hydrocarbons.

Many polycyclic aromatic hydrocarbons (PAHs) have been identified as cancer-inducing chemicals for animals and/or humans. Also, there is sufficient evidence that exposures in the occupational settings are carcinogenic or probably carcinogenic to human. Engine exhaust and used engine oils are major PAH sources in engine repair workshops and traffic. Analysis of micronucleus (MN) in exfoliated buccal cells is a sensitive method for monitoring genetic damage in human populations. In our study, we used three different occupational groups (Group 1; engine repair workers, Group 2; taxi drivers, Group 3; traffic police) and two controls (Control I for Group 1 and Control II for Group 2 and Group 3) for the exposed groups. We analysed MN frequencies in exfoliated buccal cells and compared the exposed groups (Group 1; n=34, Group 2; n=17, Group 3; n=15) and subjects not occupationally exposed to PAH (Control I; n=28, Control II; n=20). The mean (+/-S.D.) MN (%) frequencies in exfoliated buccal cells from Group 1 and Control I were 0.07+/-0.05 and 0. 05+/-0.04, respectively (p>0.05; Table 2). The mean (+/-S.D.) MN (%) frequencies in exfoliated buccal cells from Group 2, 3 and Control II were 0.12+/-0.05, 0.10+/-0.05 and 0.03+/-0.03, respectively (p<0. 0001, p<0.05; Table 2) Smokers and nonsmokers do not differ with respect to the incidence of MN in all groups.

Urinary cyclophosphamide excretion and micronuclei frequencies in peripheral lymphocytes and in exfoliated buccal epithelial cells of nurses handling antineoplastics.

In this study, urinary cyclophosphamide (CP) excretion rate, as well as micronuclei (MN) in peripheral lymphocytes and in buccal epithelial cells were determined for 26 nurses handling antineoplastics and 14 referents matched for age and sex. In urine samples of 20 out of 25 exposed nurses CP excretion rate was found in a range of 0.02-9.14 microg CP/24 h. Our results of the analyses of CP in urine demonstrates that when the nurses were handling CP (and other antineoplastic drugs) this particular compound was observed in urine. The mean values (+/-SD) of MN frequencies (%) in peripheral lymphocytes from the nurses and controls were 0.61 (+/-0. 32) and 0.28 (+/-0.16), respectively (p<0.01). The mean value (+/-SD) of MN frequency (%) in buccal epithelial cells of nurses was 0.16 (+/-0.19) and also mean MN frequency in buccal epithelial cells for controls was found to be as 0.08 (+/-0.08), (p>0.05). Age, sex and smoking habits have not influenced the parameters analyzed in this study. Handling time of antineoplastics, use of protective equipment and handling frequency of drugs have no effect on urinary and cytogenetic parameters analyzed. No correlation was found between the urinary CP excretion and the cytogenetic findings in nurses. Neither could we find any relationship between two cytogenetic endpoints. Our results have identified the possible genotoxic damage of oncology nurses related to occupational exposure to at least one antineoplastic agent, which is used as a marker for drug handling. As a whole, there is concern that the present handling practices of antineoplastic drugs used in the several hospitals in Ankara will not be sufficient to prevent exposure.

Cytogenetic biomonitoring of workers exposed to bitumen fumes.

Bitumen samples and fumes consist essentially of polycyclic hydrocarbons (PAH) and their derivatives, some of which are known to be carcinogenic or co-carcinogenic in animals. The level of total PAH is low when compared with coal-tar products. There is very limited data on possible health risk from exposure to bitumen fumes in workers. In this study, sister-chromatid exchange (SCE), micronuclei (MN) and high frequency of SCE cells (HFCs) were determined for 28 workers exposed to bitumen fumes and 28 control subjects. Urinary 1-hydroxypyrene (1-OHP) excretion was used as a biomarker of occupational exposure to PAH. The mean value of 1-OHP excretion of workers was 0.78+/-0.46 micromol/mol creatinine and for controls 0.52+/-0.44 micromol/mol creatinine (p<0.05). The mean values of SCE per cell and the frequency ( per thousand) of MN in peripheral lymphocytes from the workers and controls were 5.13+/-0. 64, 4.71+/-0.67, and 2.25+/-0.42, 1.79+/-0.32 respectively (p<0.05, p<0.0001). The mean value of HFCs for workers and controls were 7. 85+/-2.3 and 7.05+/-3.16, respectively (p>0.05). Our data reveal that bitumen fumes during road paving operations are absorbed by workers and that bitumen fume exposure is able to significantly induce cytogenetic damage in peripheral lymphocytes of workers after controlling some possible confounding factors, such as age, sex and smoking habits.

Serum uric acid levels in cardiovascular diseases.

OBJECTIVE: Comparison of the serum uric acid levels of healthy people (n=71) and patients with cardiovascular diseases (CVD) (n=62). SUBJECTS AND METHODS: The patients included had either experienced acute myocardial infarction (AMI) (n=31), atherosclerosis (AT) (n=23) or ischaemia (n=8). The mean values (x+/-SD) of serum uric acid levels of the control group, the patients with CVD as a whole, and patients with AMI, AT and ischaemia were 4.15+/-0.45 mg%, 5.6+/-2.06 mg%, 5.96+/-2.60 mg%, 5.38+/-1.22 mg% and 4.94+/-1.40 mg%, respectively. A statistically higher level of serum uric acid was found in the controls compared to the CVD patients (P < 0.05). CONCLUSION: The higher serum uric acid levels found in CVD patients suggests that any protective antioxidant effect which uric acid has is overwhelmed by other negative effects on pathogenesis.

Biological monitoring of young workers exposed to polycyclic aromatic hydrocarbons in engine repair workshops.

Several polycyclic aromatic hydrocarbons (PAHs) are carcinogenic in rodents, while exposure to these compounds has been associated with various types of human cancer. Engine exhaust and used engine oils are major PAH sources in engine repair workshops. Urinary 1-hydroxypyrene (1-OHP) levels and some genotoxicity parameters (sister-chromatid exchange, SCE; micronucleus, MN) have been compared among engine repair workers (n = 61, age: between 13 and 18) and workers not occupationally exposed to PAH (n = 30, age: between 13 and 19). The mean value (+/- S.E.) of urinary 1-OHP excretions of workers was 4.71 +/- 0.53 micromol/mol creatinine and also mean urinary 1-OHP for controls was found to be as 1.55 +/- 0.28 micromol/mol creatinine. The mean values (+/- S.E.) of SCE frequency per cell in peripheral lymphocytes from the workers and controls were 4.47 +/- 0.09 and 4.06 +/- 0.16, respectively (p < 0.05). The mean (+/- S.E.) MN (per thousand) frequencies in peripheral lymphocytes from the workers and controls were 1.87 +/- 0.04 and 1.56 +/- 0.06, respectively (p < 0.0001). The effect of smoking for the above parameters were also evaluated.

Evaluation of genotoxic potential of styrene in furniture workers using unsaturated polyester resins.

Styrene is a widely used chemical, mostly in making synthetic rubber, resins, polyesters, plastics and insulators. Increasing attention has been focused on this compound since experiments using cytogenetic end-points have implicated styrene as a potential carcinogen and mutagen. In order to perform biological monitoring of genotoxic exposure to styrene monomer, we evaluated the urinary thioether (UT) excretion, and sister chromatid exchanges (SCEs) and micronuclei (MN) in peripheral lymphocytes from 53 furniture workers employed in small workplaces where polyester resin lamination processings were done and from 41 matched control subjects. The mean air concentration of styrene in the breathing zone of workers was 30.3 ppm. As a metabolic marker for styrene exposure, mandelic acid + phenylglyoxylic acid was measured in the urine and the mean value was 207 mg/g creatinine. The mean +/- SD value of UT excretions of workers was 4.43 +/- 3.42 mmol SH-/mol creatinine and also mean UT for controls was found to be a 2.75 +/- 1.78 mmol SH-/mol creatinine. The mean +/- SD/cell values of SCE frequency in peripheral lymphocytes from the workers and controls were 6.20 +/- 1.56 and 5.23 +/- 1.23, respectively. The mean +/- SD frequencies (%o) of MN in the exposed and control groups were 1.98 +/- 0.50 and 2.09 +/- 0.35, respectively. Significant effects of work-related exposure were detected in the UT excretion and SCEs analyzed in peripheral blood lymphocytes (p < 0.05 and p < 0.01, respectively). The MN frequency in lymphocytes from the styrene-exposed group did not differ from that in the controls (p > 0.05). Effect of smoking, age and duration of exposure on the genotoxicity parameters analyzed were also evaluated. In conclusion, although our data do not demonstrate a dose-response relationship, they do suggest that styrene exposure was evident and that this styrene exposure may contribute to the observed genotoxic damage in furniture workers.

Serum carotenoids and uric acid levels in relation to cancer.

We studied the levels of serum total carotenoids and uric acid in newly diagnosed cancer cases. The levels of carotenoids and uric acid in serum samples from 94 subjects with cancer affecting different sites (21 breast, 26 head and neck, 13 lung, 17 genitourinary and 17 other sites) were compared with those of 92 controls who were matched for age, sex, Quetelet index and smoking history. Mean (+/- SE) levels of carotenoids were significantly lower among the cases than the controls (51.41 +/- 3.32 vs. 102.75 +/- 4.52 micrograms/dl, P < 0.001), when all the different sites were considered together. The mean (+/- SE) uric acid levels among cases and controls were 5.14 +/- 0.16 mg/dl and 4.21 +/- 0.18 mg/dl (P < 0.001), respectively. It was of interest that patients with genitourinary cancer had the lowest serum carotenoids levels, and the highest levels were found in patients with breast cancer. These results are informative but do not establish a causal link. There was no apparent association between serum urate levels and cancer site. The data presented here do not provide support for the protective antioxidant properties of uric acid in cancer.

Some immunological parameters in workers occupationally exposed to n-hexane.

1. To estimate the quantitative relation between exposure to airborne n-hexane and various markers of immune function, 35 male workers were examined and compared with unexposed controls. 2. Urinary 2,5-hexanedione concentrations were significantly higher in the exposed group than in the unexposed. 3. A significant suppression was observed in the serum immunoglobulin (IgG, IgM and IgA) levels between two populations. Also, a significant correlation was found between urinary 2,5-hexanedione concentrations and serum Ig level of the exposed group. 4. No significant difference between white blood cell counts was found in the two groups.