Cytokinesis-blocked micronucleus cytome and comet assays in peripheral blood lymphocytes of workers exposed to lead considering folate and vitamin B12 status.

In human biomonitoring, factors such as age, gender, smoking habit and alcohol consumption are usually considered and identified as agents that exert an impact on genotoxicity biomarkers. However, as a rule, factors like micronutrient status are not considered in biomonitoring studies. This paper reports on genotoxic damage in Pb-exposed workers using data obtained from the cytokinesis-block micronucleus (CBMN) cytome assay and alkaline comet assay with silver staining, considering folate and vitamin B12 nutritional status. Analysis of the results showed that the Pb-exposed group presented a 24-fold higher Pb content in the blood compared to controls. The Pb-exposed workers presented significantly greater micronuclei (MNi) counts (Z=7.9583; p<0.0001) and DNA damage, assessed by the comet assay (DF: Z=7.7056; p<0.0001 and DI: Z=7.4749; p<0.0001), but no correlation with Pb blood concentrations were detected. These two groups did not differ significantly concerning folate and vitamin B12 levels. Regarding folate, it is possible that this similarity is associated with folic acid flour-enrichment, introduced in Brazil in 2004 to prevent neural tube defects. The mean folate level obtained in the Pb-exposed group was 6.18ng/ml. The subgroup of individuals with serum folate levels equal to or higher than the mean presented significantly higher MNi (Z=2.3776; p=0.017) and nucleoplasmic bridge (NPB) frequencies (Z=1.9850; p=0.047) in peripheral blood lymphocytes. A significant positive correlation was observed between the age of Pb-exposed workers and MNi frequencies (Gamma=0.3328; p<0.001), NPBs (Gamma=0.1832; p<0.042) and DNA damage assessed by the comet assay (DF: Gamma=0.1764; p=0.035 and DI: Gamma=0.11852; p=0.028). These findings suggest that high folate levels alone do not guarantee protection against genotoxic damage. Moreover, folic acid supplementation should be studied using more efficient approaches to determine safe amounts and potential deleterious effects.

Genotoxicity evaluation of three benzopyrans from Hypericum polyanthemum.

In the present study we used the micronuclei test and the comet assay in mice to investigate the genotoxic and mutagenic effects of three benzopyrans--6-isobutyryl-5,7-dimethoxy-2,2-dimethyl-benzopyran (HP1); 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethyl-benzopyran (HP2); and 5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethyl-benzopyran (HP3)--isolated from Hypericum polyanthemum. No significant difference in polychromatic erythrocyte (PCE) percentage between the vehicle group and groups treated with HP1, HP2, or HP3 was detected, indicating no toxicity to the bone marrow of the animals. Only HP1 increased the frequency of micronucleated cells (MNPCEs) in bone marrow sampled after 24 h in comparison with the vehicle group, suggesting a weak mutagenic effect. The damage index and damage frequency did not show a significant increase after treatment with HP1, HP2, or HP3 in comparison with the vehicle group. The antitumor activity previously reported in vitro for these benzopyrans, the lack of acute toxicity, the MN induction only for HP1, and the relatively low DNA damage make all compounds good candidates for in vivo studies on antitumor action.

Micronucleus induction in mouse polychromatic erythrocytes by an X-ray contrast agent containing iodine.

In this article, the authors report the results of in vivo studies on bone marrow polychromatic erythrocytes (PCE) from mice treated with Urografina®292 (a mixture of sodium amidotrizoate and meglumine amidotrizoate) and with purified sodium amidotrizoate and meglumine amidotrizoate separately or in combination at the same ratio and concentration as that of the highest dose of Urografina®292 used in the experiment. The results showed that Urografina®292 significantly increased the frequencies of micronucleated polychromatic erythrocytes (MNPCEs) in both male (p=0.0082 and p=0.0062) and female (p=0.0350 and p=0.0101) mice treated with doses of 14.3 and 20.0 ml/kg body weight, respectively. When lower doses were used (5.7 and 8.6 ml/kg body weight), the treated mice did not show any significant increase in the frequencies of MNPCEs compared with the negative control group. The same result was observed for both male and female animals treated with purified sodium amidotrizoate and meglumine amidotrizoate separately or in combination. In addition, there was a significant positive correlation between the Urografina®292 doses used and the frequency of micronuclei. These results supported the hypothesis that small amounts of aryl amines present in all X-ray contrast agents containing diatrizoate and closely related triiodobenzoates were responsible for genotoxicity. The frequencies of PCEs in treated animals were determined to estimate the toxicity of Urografina®292, sodium amidotrizoate, and meglumine amidotrizoate to bone marrow, and the results indicated that they did not show any significant difference compared with the negative control group. The fact that mutagenic agents are also generally carcinogenic contributes to the concern with regard to the possible long-term risks of these agents in case of patients who are exposed to iodine-containing X-ray contrast agents during radiodiagnostic procedures.

Plumbemia em trabalhadores da indústria de reciclagem de baterias automotivas da Grande Porto Alegre, RS / Blood lead levels in the battery recycling industry of the metropolitan region of Porto Alegre, RS

A reciclagem de baterias pode contaminar o ar, o solo e a água, não só no lugar de processamento, mas também nas regiões circunvizinhas, sendo que os resíduos permanecem no local mesmo após o término da atividade. No presente artigo descrevemos os resultados da avaliação da plumbemia em 53 operários que trabalhavam com reciclagem de baterias automotivas e em 53 indivíduos sem história de exposição. Os dados obtidos foram comparados e discutidos em relação às normas do Ministério do Trabalho (MT) e da Occupational Safety and Health Administration (OSHA). A plumbemia no sangue do grupo controle foi de 2,44±1,15 µg/dl e, no grupo exposto, de 59,43±28,34 µg/dl, sendo que 79,2 por cento dos indivíduos mostraram níveis acima do valor de referência (até 40 µg/dl). Estudos recentes recomendam estratégias para prevenir a intoxicação com chumbo: identificação, eliminação ou controle da fonte, monitoração da exposição e respectivos danos e um programa de recompra de baterias usadas das por parte da indústria de origem.

Battery recycling may contaminate soil, air and water not only at the processing site but also in the neighboring areas, inasmuch as the residues remain at the site even after the end of the activity. In the present article, we describe the results of plumbism evaluation in 53 individuals that work with car battery recycling and 53 individuals without history of lead exposure. The obtained data were compared and discussed according to the regulations of Brazilian Ministry of Labor and OSHA (Occupational Safety and Health Administration). Blood lead levels in the control group were 2.44 ± 1.15 µg/dl and 59.43 ± 28.34 µg/dl in the exposed group. 79.2 percent of the individuals presented levels above the reference value (40 µg/dl). Recent studies recommend strategies to prevent lead intoxication: source identification, control or elimination, monitoring of environmental exposure and hazards and a buy-back program of used batteries by the industry of origin.

Chemoprotective effect of cysteamine against the induction of micronuclei by methyl methanesulfonate and cyclophosphamide

Cysteamine or 2-mercaptoethylamine (MEA) is an aminothiol with a well-known radioprotective action. No specific information is available in the literature about the possible chemoprotective action of MEA against genotoxic chemical agents. This paper presents the results of studies on the ability of MEA to protect mouse bone marrow polychromatic erythrocytes against the induction of micronuclei by alkylating agents such as methyl methanesulfonate (MMS) and cyclophosphamide (CP). We observed that MEA administered intraperitoneally 30 min before or 30 min after the administration of MMS or CP significantly reduced the frequency of micronucleated polychromatic erythrocytes (MNPCEs) induced by the alkylating agents. When MEA was administered in combination with MMS or CP the reduction in the frequency of MNPCEs did not reach statistically significant levels, although it reached values close to significance. With respect to the polychromatic erythrocyte/normochromatic erythrocyte (PCE/NCE) ratio, we observed that MEA did not provide significant protection against the bone marrow toxicity induced by CP.

Micronuclei in peripheral blood lymphocytes of workers exposed to lead.

Lead plays an important role in many industrial processes. Although highly useful to man, lead has various types of toxic effects. There is constantly growing evidence of a relationship between the induction of chromosome breaks and an increased risk of onset of cancer. However, available data about the possible genotoxic and carcinogenic action of lead are conflicting. In this report we present the results of studies on lead concentrations in blood and the respective micronucleus frequencies in peripheral blood lymphocytes from workers employed in the recycling of automotive batteries in the surroundings of Porto Alegre, Brazil. We observed that in the occupationally exposed group, both lead concentration in peripheral blood and micronucleus frequency in lymphocytes were significantly higher compared to control (Z=6.35, P<0.0001 and Z=4.47, P<0.0001). The nuclear division index (NDI) values were significantly higher in the control group than in the exposed group (Z=2.13, P=0.0330), indicating a possible effect of Pb on nuclear proliferation. We also detected a negative correlation between micronuclei and progression of nuclear division (tau=-0.312, P=0.0129). There were no changes in micronucleus frequency between smoking and non-smoking workers exposed to lead (Z=0.03, P=0.9790). The only difference found between the groups of smokers and non-smokers was with respect to NDI, whose values were significantly higher among non-smokers (Z=1.98, P=0.0481).