Induction of excision repairable DNA lesions in lymphocytes exposed to lead and ALA in vitro.

Numbers of studies have been carried out on the potential of lead genotoxicity. The mechanisms of lead genotoxicity are not fully known but partly attributed to the formation of highly reactive oxygen metabolites (ROM). However, lead ions have no ability to generate ROM. In this study, we have investigated the ability of lead and ALA to induce excision repairable DNA lesions by using cytosine arabinoside or cytokinesis block micronucleus (ARA-C/CBMN) assay. N-methyl-N-nitrosourea was used as a positive control which is a mutagen and known to induce excision repair. The results of the ARA-C/CBMN assay show that ALA exposures have significantly (p < 0.01) increased the ratio of excision repairable DNA lesions in peripheral blood lymphocytes; however, lead have not. Accordingly, accumulation of ALA should be considered as an effective partner of lead induced DNA damage in lead exposure.

The influence of melatonin and N-acetylcysteine in delta-aminolevulinic acid and lead induced genotoxicity in lymphocytes in vitro.

As is well known from earlier studies, the genotoxic effect of lead exposure was partly attributed to the formation of the highly reactive oxygen metabolites (ROMs) in the blood. However, lead ions have no ability to generate ROMs. Therefore, the recently published studies paid more attention to the role of delta-aminolevulinic acid (ALA) accumulation in lead-induced DNA damage. If the above-mentioned assumptions were taken into consideration, it seemed a reasonable approach to study the possible protective effects of antioxidants against genotoxic effects of lead. According to our results, N-acetylcysteine (NAC) and melatonin (MEL) were able to reduce significantly (p<0.05) the lead- and ALA-induced sister chromatid exchange frequencies in human lymphocytes in vitro. In spite of a relative reduction in the lead- and ALA-induced micronucleus formation in human lymphocytes, the reduction was not statistically significant (p>0.05). These results could be evaluated as supportive evidence for the hypothesis that increased antioxidant capacity of cells might fortify the efficiency of protective pathways against cytogenetic damage in lead exposure.

TYMS and DPYD polymorphisms in a Turkish population.

OBJECTIVE: The thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) enzymes affect the outcome of 5-fluorouracil (5-FU)-based chemotherapy. Genetic polymorphisms of the thymidylate synthase (TYMS) and dihydropyrimidine dehydrogenase (DPYD) genes that may affect chemotherapy are described. The aim of this study was to determine the frequencies of TYMS and DPYD polymorphisms in healthy Turkish individuals. METHODS: Genotyping analyses of the promoter enhancer region of TYMS (TSER) and the exon 14-skipping mutation of the DPYD (DPYD*2A) genes were conducted in 250 unrelated, healthy volunteers from the central region of Turkey using a PCR-based assay. RESULTS: The distribution of the TSER*2/*2, *2/*3 and *3/*3 genotypes were 17.6%, 48.8%, and 33.6%, respectively. The frequencies of the TSER*2 and *3 alleles in the Turkish population were 0.42 and 0.58, respectively. No individuals with the variant DPYD*2A allele were identified in the study group. CONCLUSION: The frequency of the TSER*3 allele among members of the Turkish population was similar to frequencies observed in other Caucasian populations but was lower than those found in Japanese and Chinese populations.

Correlation between lead exposure indicators and sister chromatid exchange (SCE) frequencies in lymphocytes from inorganic lead exposed workers.

Inorganic lead exposure was studied in 31 volunteers employed in storage battery plant. The genotoxicity of lead was measured in terms of sister chromatid exchange (SCE). Erythrocyte delta-aminolevulinic acid dehydrogenase (ALAD) activity, urinary delta-aminolevulinic acid (U-ALA), and blood lead levels (PbBs) were also determined to evaluate some possible relations between these lead exposure indicators and the observed SCE frequencies. Blood lead concentration of 36.31 microg/dl was determined as an average level in the workers. Consequently decreased ALAD activity in erythrocytes and increased U-ALA excretion was observed in statistically higher PbBs when compared with the control group. A statistically significant correlation was observed between the PbBs and SCE frequencies (p < 0.05). Moreover, the correlation between U-ALA excretion and SCE frequencies (p < 0.01) was relatively higher than the correlation between PbBs and SCE frequencies. These results might indicate a possible mechanism of ALA mediation in the genotoxic effects of lead.

Urinary excretion of lead and delta-aminolevulinic acid in workers occupationally exposed to tetraethyl lead.

Forty-nine refinery workers and 50 motor mechanics were selected and examined for total lead (PbT), inorganic lead (PbI), and delta-aminolevulinic acid (ALA) in urine. The worker groups were exposed to tetraethyl lead (TEL) mainly by inhalation, but motor mechanics received additional exposure by skin because of hand cleansing with gasoline. The levels of urinary ALA (ALA-U) and urinary PbT (PbT-U) in refinery workers and motor mechanics were found to be significantly higher than the control group (p<0.05). The correlation between the ALA-U and PbT-U was found significant in both worker groups (p<0.001); however, relatively higher positive correlation was found between ALA-U and urinary inorganic lead (PbI-U) in TEL-exposed workers.

Biological monitoring of lead in workers exposed to tetraethyllead.

The excretion of inorganic, and total lead was investigated in the urine of workers who were exposed to tetraethyllead (TEL) at gasoline stations. Concentrations of total and inorganic lead after chelation-extraction were determined by flame atomic absorption spectrophotometry (FAAS) in combination with a slotted quartz tube. The limit of detection was 5.2 x 10(-3) micrograms Pb/ml; average total lead and inorganic lead concentrations in the urine of workers were 79.0 (range 22.6-158.9 micrograms Pb/g creatinine) and 37.3 micrograms Pb/g creatinine (range 5.1-121.0), respectively. In the control group, the mean of the urinary total lead and inorganic lead levels were 5.5 and 3.9 micrograms Pb/g creatinine, respectively. The difference between total and inorganic lead concentrations could be due to organic lead present in the urine.