Pyridoxine deficiency modulates benzene inhalation-induced hematotoxicity associated with hepatic CYP2E1 activity in B6C3F1 mice.

Pyridoxine is a co-factor in many enzymatic reactions and impacts of deficiency have been observed in affected populations. A possible modifying effect of pyridoxine deficiency on benzene toxicity was assessed in male B6C3F1 mice fed either a pyridoxine-deficient diet or a control diet. This treatment was combined with benzene inhalation exposure (100 ppm) or no benzene treatment. Pyridoxine-deficient mice exposed to 100 ppm benzene had significantly lower body, thymus and spleen weights. While total white blood cell counts, percentage of lymphocytes, hematocrit and hemoglobin levels were lower, the percentage of neutrophils was significantly higher in deficient and benzene-exposed mice compared to non-exposed controls. Hepatic CYP2E1 protein expression and activity in the deficient and exposed mice were also significantly higher compared to the non-exposed controls. A significant correlation between CYP2E1 activity and several hematological parameters was observed. These results demonstrated that pyridoxine deficiency significantly impacted benzene-induced hematotoxicity. Moreover, the observed agonistic effect of pyridoxinedeficiency and benzene inhalation exposure on CYP2E1 would seem to indicate an involvement of metabolism, but this needs to be further assessed.

Effects of topical exposure to a mixture of chlorpyrifos, cypermethrin and captan on the hematological and immunological systems in male Wistar rats.

Most Thai orchid farmers heavily used pesticide mixtures, and were shown to have various hematologic/immunologic alterations. The present study investigated the effect of exposure of male Wistar rats to a mixture of three pesticides (chlorpyrifos, cypermethrin and captan) that are most often used by the farmers. Three groups of 10 rats were dermally exposed to three different doses (high, middle and low) for 28 consecutive days. The rats showed significant changes in body, liver, kidneys and adrenals weights. Significant changes were observed in various biological parameters including hematotoxicity (increased leukocyte and platelet counts, percent neutrophil, decreased RBC count, percent lymphocyte and eosinophil), hepatotoxicity (increased serum AST, decreased serum ALP, cholesterol, triglyceride, serum protein and albumin), and immunotoxicity (decrease in numbers of NK cells, decrease splenic proliferative response to LPS, and increase in serum IgG). These results confirm the potential health danger of exposure to these pesticide mixtures in orchid farmers.

The effects of pyridoxine deficiency and supplementation on hematological profiles, lymphocyte function, and hepatic cytochrome P450 in B6C3F1 mice.

Pyridoxine, a B(6) vitamin, is a co-factor in a variety of enzymatic reactions involved in intermediary metabolism. The effects of pyridoxine deficiency and supplementation on hematological profiles, lymphocyte function, and hepatic CYP1A1 and CYP2E1 were investigated in B(6)C(3)F(1) mice fed a diet containing either 0 (i.e., pyridoxine-deficient diet, [PD]); or 7 mg pyridoxine-HCl/kg (i.e., control diet, [CD]) for 8 or 13 weeks followed by administration of 500 mug pyridoxine-HCl (IP) daily for either 2 (PD-S2 and CD-S2) or 3 (PD-S3 and CD-S3) consecutive days. Results demonstrated that erythrocyte aspartate aminotransferase activity coefficient (EAST-AC) values, which reflect host pyridoxine status, were significantly higher in PD mice than in CD mice, and dropped to control levels after supplementation. PD mice had significantly reduced weight gains, mean corpuscular volume (MCV), hemoglobin (HGB), and hematocrit (HCT) levels compared to CD mice after 8 and 13 weeks on the prescribed diet. In addition, PD mice had significantly lower circulating levels of total white blood cells, but higher red blood cell numbers after 8 weeks (compared to CD mice). Pyridoxine supplementation for 3 days restored HGB levels in PD mice to that of the unsupplemented CD controls; HCT, MCV and MCH levels were also increased in PD-S3 mice compared to their unsupplemented PD counterparts, but failed to reach comparable levels to those seen in mice fed a control diet. The pyridoxine-deficient diet also resulted in decreased mitogen stimulated T-lymphocyte proliferation after a 13-week feeding regimen and increased hepatic CYP1A1 activity that was reversed by pyridoxine supplementation. These studies demonstrate in a murine model that pyridoxine deficiency can cause multiple alterations that, in many cases, can be reversed by supplementation.

Exposure to genotoxins present in ambient air in Bangkok, Thailand--particle associated polycyclic aromatic hydrocarbons and biomarkers.

Exposure to genotoxic compounds in ambient air has been studied in Bangkok, Thailand, by analysis of polycyclic aromatic hydrocarbons (PAHs) associated with particles and using different biomarkers of exposure. Eighty-nine male, non-smoking Royal Thai police officers were investigated. The police officers were divided into a high exposure group (traffic police) and low exposure (office duty). Particulate matter was collected using personal pumps (2 l/min) and the eight carcinogenic PAHs were analysed by standard procedures. The traffic police was exposed to a 20-fold higher level of total PAHs than office police (74.25 ng/m3 vs. 3.11; P= 0.001). A two-fold variation was observed between the different police stations. The major PAHs in all groups was benzo[g,h,l]pyrelene. Large inter-individual differences in biomarker levels were observed, but the level of all markers was statistically significantly higher in the traffic police group than in the office group. The level of 1-hydroxypyrene (1-HOP) was 0.181+/-0.078 (range 0.071-0.393) micromol/mol creatinine in the traffic group and 0.173+/-0.151 (P = 0.044) in the office group. The bulky carcinogen DNA-adduct level, determined by P32-post-labelling, was 1.6+/-0.9 (range 0.4-4.3) adducts/10(8) nucleotides in the traffic group and 1.2+/-1.0 (0.2-4.9) in the office group (P = 0.029; Mann-Whitney U-test). The serum PAH-albumin adduct level was 1.76 (0.51-3.07) fmol adducts/microg albumin in the traffic group and 1.35+/-0.77 (0.11-3.45; P = 0.001) in the office group. Lower biomarker levels were observed during the period when the traffic police officers were wearing a simple facemask, indicating that these masks protect against particle-associated PAHs. No statistically significant correlations were observed between biomarker levels and the level of individual PAHs or total PAH. Our data show, that people in Bangkok, who spend most of the day outside air-conditioned offices, are exposed to high levels of genotoxic PAHs. However, for people who spend their working day in offices, the exposure is similar to people living in other metropolitan areas.