Toxicology and Industrial Health

Kilburn, Kaye H ;Thrasher, Jack D ;Gray, Michael R

doi: 10.1177/0748233710369126pmid: 20504829

Forty-nine adults living in Lovington, Tatum, and Artesia, the sour gas/oil sector of Southeastern New Mexico, were tested for neurobehavioral impairment. Contributing hydrogen sulfide were (1) an anaerobic sewage plant; (2) two oil refineries; (3) natural gas/oil wells and (4) a cheese-manufacturing plant and its waste lagoons. Comparisons were to unexposed Wickenburg, Arizona, adults. Neurobehavioral functions were measured in 26 Lovington adults including 23 people from Tatum and Artesia, New Mexico, and 42 unexposed Arizona people. Participants completed questionnaires including chemical exposures, symptom frequencies and the Profile of Mood States. Measurements included balance, reaction time, color discrimination, blink reflex, visual fields, grip strength, hearing, vibration, problem solving, verbal recall, long-term memory, peg placement, trail making and fingertip number writing errors (FTNWE). Average numbers of abnormalities and test scores were adjusted for age, gender, educational level, height and weight, expressed as percent predicted (% pred) and compared by analysis of variance (ANOVA). Ages and educational attainment of the three groups were not statistically significantly different (ssd). Mean values of Lovington residents were ssd from the unexposed Arizona people for simple and choice reaction times, balance with eyes open and closed, visual field score, hearing and grip strength. Culture Fair, digit symbol substitution, vocabulary, verbal recall, peg placement, trail making A and B, FTNWE, information, picture completion and similarities were also ssd. The Lovington adults who averaged 11.8 abnormalities were ssd from, Tatum—Artesia adults who had 3.6 and from unexposed subjects with 2.0. Multiple source community hydrogen sulfide exposures impaired neurobehavioral functions.

Kostka, Grażyna ;Urbanek-Olejnik, Katarzyna ;Wiadrowska, Bożena

doi: 10.1177/0748233710369124pmid: 20504828

Peroxisome proliferators (PPs)-induced DNA hypomethylation has been proposed as a mechanism of their toxicity, including carcinogenic action. The effect of di-butyl phthalate (DBP), a known peroxisome proliferators, on the methylation level of the c-myc promoter region in rat liver was studied. Changes in the methylation status of the c-myc gene were correlated with changes in DNA synthesis, DNA methyltransferase (DNMTs) activity and liver weight. Male Wistar rats received DBP in one, three or fourteen daily oral doses of 1800 mg/kg body weight (b.w.) × day—1 (this dose is close to the dose that increases the numbers of peroxisomes in male Wistar rats). We have demonstrated that DBP decreased the methylation of the c-myc gene. Cytosine hypomethylation in the analyzed CpG sites of the c-myc gene promoter occurred during the whole period of study, although after 14 doses of DBP the difference from control was only on the borderline of significance (p = 0.066). An increase in DNA synthesis was only observed after 24 hours of treatment with DBP, and it preceded liver growth. We hypothesize that DBP-induced demethylation of the c-myc gene was an active mechanism, not associated with DNMTs activity and DNA replication.

Ghosh, Manosij ;Biswas, Dhrubojyoti ;Mukherjee, Anita

doi: 10.1177/0748233710369125pmid: 20504830

People live in the mountains distributed across the world and are exposed to reduced inspired oxygen and lower barometric pressure along with other factors that lead to high-altitude diseases. The present study was conducted to examine what extent of marketed medicines used in the management of high-altitude sickness has been tested for their genotoxic activity. Comet assay or the single-cell gel electrophoresis was utilized to evaluate genotoxicity of the six medicines on human peripheral whole blood cells and isolated lymphocytes at the concentrations 250 μg/mL, 500 μg/mL and 1 mg/mL. The comet assay endpoints included percentage Tail DNA (% Tail DNA) and olive tail moment (OTM) as they were considered to be sensitive and reliable scores across different laboratories. The results show that dexamethasone, deriphylline and furosemide can induce significant DNA damage in human whole blood and lymphocytes alike. Acetazolamide, ibuprofen and nifedipine show no genotoxic effect, neither on human whole blood nor on human lymphocytes. Taking into account the results of genotoxicity, it will be a prudent choice to restrict the use of these compounds for longer periods, until more information on the in vitro mutagenicity and in vivo genotoxicity studies are available.

Ercan, Sevim ;Öztürk, Nihal ;Celik-Ozenci, Ciler ;Gungor, Nazli Ece ;Yargicoglu, Piraye

doi: 10.1177/0748233710369665pmid: 20504823

Sodium metabisulfite (Na 2S2O5) is used as an antioxidant and antimicrobial agent in a variety of drugs and functions as a preservative in many food preparations. This study was performed to elucidate the dose-dependent effects of sodium metabisulfite ingestion on rat gastric tissue apoptotic changes and lipid peroxidation. Forty male wistar rats, aged 3 months were used. They were randomly divided into four groups: control (C), the group treated with Na2S2O5 (10 mg/kg; S1), the group treated with Na2S2O5 (100 mg/kg; S2), the group treated with Na2S2O5 (260 mg/kg; S3). Na 2S2O5 was given by intragastric intubation for 35 days. In the S2 and S3 groups, malondialdehyde (MDA) levels increased markedly when compared with the control group. High doses of sulfite administration elevated number of apoptotic cells both in mucosa and submucosa layers of stomach in parallel with increased MDA levels. These results suggest that sodium metabisulfite increased lipid peroxidation and thus number of apoptotic cells on gastric tissue in dose-dependent manner.

Oktar, Süleyman ;Gökçe, Ahmet ;Aydin, Mehmet ;Davarci, Mürsel ;Meydan, Sedat ;Oztürk, Oktay Hasan ;Koç, Ahmet

doi: 10.1177/0748233710369666pmid: 20504824

Methotrexate is used to treat certain types of cancer of the breast, skin, head and neck, or lung. Methotrexate can cause serious or life-threatening side effects on liver, lungs, kidneys, and immune system. Methotrexate chemotherapy causes testicular damage in humans. The aim of this study was to investigate the possible protective role of erdosteine on testicular toxicity of methotrexate in mice. Twenty-six male mice were divided into four groups as follows: group 1, control; group 2, erdosteine-treated; group 3, methotrexate-treated; and group 4, methotrexate + erdosteine treated. On the first day of experiment, a single dose of methotrexate was intraperitoneally administered to groups 3 and 4, although a daily single dose of erdosteine was orally administered to group 2 and 4 for 7 days. At the end of the experiment, the testes of the animals were removed and weighed. The levels of total antioxidant capacity and total oxidative stress, and myeloperoxidase activity in the methotrexate group were higher than the control group (p<0.05). Lipid peroxidation levels were not changed in methotrexate group compared with control group. In conclusion, erdosteine could effectively protect the testes in methotrexate-induced toxicity.

Tripathi, Sarojni ;Srivastav, Ajai Kumar

doi: 10.1177/0748233710371110pmid: 20504822

Wistar rats (male) were divided into 3 groups — group A (GA) served as control, group B (GB) were daily administered chlorpyrifos (Anu Products Ltd., India) orally at a dose of 5 mg/kg b wt. and animals in group C (GC) received daily an oral administration of chlorpyrifos at a dose of 10 mg/kg b wt. Rats were sacrificed on 1st, 2nd, 4th, 6th and 8th week after initiation of the experiment. Kidneys were extirpated and fixed in aqueous Bouin’s solution. The tissues thus fixed were routinely processed for histological studies. The present study showed that the histopathological changes were caused in kidney of rats by chlorpyrifos administration. The changes noticed were mainly the shrinkage of glomerulus at initial stage of treatment, the tubular dilation, the glomerular hypercellularity, hypertrophy of tubular epithelium, degeneration of glomerulus and renal tubules, deposition of eosin-positive substances in the glomerulus and renal tubules and infiltration of leucocytes. A decrease in the body weight gain was observed in chlorpyrifos-treated rats. However, variable intensities of these changes were noticed depending upon the doses and duration of the treatment.