Short Review: Benzene's toxicity: a consolidated short review of human and animal studies: Khan, Haseeb Ahmad
doi: 10.1177/0960327107083974pmid: 17984138
A large population of humans is exposed to benzene from various occupational and environmental sources. Benzene is an established human and animal carcinogen. Exposure to benzene has been associated with leukaemia in humans and several types of malignancies in animals. The exact mechanism of benzene-induced toxicity is poorly understood. It is believed that benzene exerts its adverse effects by metabolic activation to toxic metabolites. Certain benzene metabolites are genotoxic and mutagenic. This consolidated short-review is composed of human and animal studies to summarize the adverse effects of benzene with special reference to molecular mechanisms involved in benzene-induced toxicity.Human & Experimental Toxicology (2007) 26,677—685
Benzene's toxicity: a consolidated short review of human and animal studies by HA Khan: Snyder, R.
doi: 10.1177/0960327107083975pmid: 17984139
Khan's review is a brief summary of the complex field of study revolving around bone marrow toxicity and leukemogenesis observed in people chronically exposed to benzene. These comments are intended to demonstrate the use of the Kahn review as a launching pad for an in-depth analysis of the several related areas that must be fully explored to understand benzene-related diseases. The accumulated evidence demonstrates that benzene-induced bone marrow damage results from the production of hematotoxins that are metabolic products of benzene metabolism. The metabolism of benzene is described with respect to the formation benzene metabolites with emphasis on phenol and hydroquinone, which are the major metabolites, the significance of the formation of glutathione conjugates, the activity of NAD(P)H:quinone oxidoreductase (NQO1), and the ring opening products. Results are shown suggesting that oxidative stress induced by benzene metabolites is likely to be a significant factor in damaging DNA in bone marrow cells. Although a variety of effects on bone marrow can be demonstrated it is not yet clear which metabolites are most important in either benzene-induced aplastic anemia or leukemia. Benzene metabolism alone is insufficient to fully describe benzene toxicity. The impact of benzene metabolites on bone marrow cells must be fully explored to determine how benzene exposure can result in decreased viability or genetic toxicity to cells in the bone marrow.Human & Experimental Toxicology (2007) 26,687—696
Determination of AChE levels and genotoxic effects in farmers occupationally exposed to pesticides: Naravaneni, Rambabu ;Jamil, Kaiser
doi: 10.1177/0960327107083450pmid: 17984143
Pesticides can cause cytogenetic effects and lower the acetyl cholinesterase (AChE) levels in farmers exposed to pesticides. In this study, 210 farmers exposed to pesticides and 160 non-exposed individuals were enrolled for determining the genotoxicity and AChE levels. The AChE levels were determined in plasma and RBC lysate from blood samples collected from farmers and control subjects. AChE (true and pseudo) estimation done by the colorimetric method revealed that there was a progressive fall in both the RBC and plasma AChE levels in exposed individuals compared to unexposed individuals, which correlated with the severity of exposure (253.5 versus 311.1 and 142.3 versus 152.1; P < 0.001). Cytogenetic studies showed an increase in DNA damage and higher chromosomal aberrations (CAs) in exposed farmers compared to the control subjects (26.13 versus 07.61 and 21.37 versus 1.52; P < 0.001). When comparing the AChE levels with DNA damage and structural CA frequencies, there was a negative linear correlation. Therefore based on these findings, it is concluded that genotoxic biomarkers like CA frequencies, DNA damage data along with AChE levels are important parameters for determining farmer's health who are exposed to pesticides in any situation.Human & Experimental Toxicology (2007) 26,723—731
Behavioral effects induced by subchronic exposure to Pb and their reversion are concentration and gender dependent: Soeiro, Aline C. ;Gouvêa, Thiago S. ;Moreira, Estefânia G.
doi: 10.1177/0960327107083016pmid: 17984144
Lead (Pb) seems to be involved in the etiology of psychological pathologies. This study investigated the effects of subchronic Pb exposure from weaning to adulthood on anxiety, depression and aggressiveness in male and female Swiss mice. Moreover, the reversibility of the effects was evaluated retesting the animals 30 days after the end of exposure. Swiss male and female mice (21 days) were exposed to 0, 50, 100 or 500 ppm of Pb, as Pb acetate, in drinking water for 70 days and were submitted to the forced swimming, tail suspension, elevated plus-maze or intruder—resident tests. Pb exposure to 50 and 500 ppm induced anti-depressant-like effect in both males and females, whereas exposure to 500 ppm induced anxiogenic effect only in males. Interruption of exposure was able to reverse the behavioral alterations in females, but not in males exposed to the highest concentration (500 ppm). Our results suggest that behavioral effects induced by subchronic exposure to Pb from weaning to adulthood and their reversion are concentration and gender dependent.[Human & Experimental Toxicology] (2007) 26, 733—739
Aluminum exposure decreases dopamine D1 and D2 receptor expression in mouse brain: Kim, Sunyoun ;Nam, Jungmin ;Kim, Kisok
doi: 10.1177/0960327107083973pmid: 17984145
Aluminum (Al) has been identified as a potential contributing factor in the etiology of several neurodegenerative disorders, but data regarding specific effects on neurotransduction, especially on dopaminergic neurotransduction, are lacking. The objective of this study was to determine the extent of expressional alterations in dopamine receptors (DRs) in two dopaminergic subtypes, D1 and D2, in low and high dose Al-treated mice. After administration of Al (four intraperitoneal injections of 30 or 60 mg/kg AlCl3·6H2O at 2 h intervals), expression of the dopamine D1-like and D2-like receptors (DRD1, DRD2) was examined in the cortex and striatum of mouse brain at bregma levels of 1.10, -0.10 and -1.34 mm. In the cortex, Al treatment decreased densities of DRD1 and DRD2 in a dose-dependent manner at all three bregma levels, especially in the high-dose Al group. Similarly, DRD1 and DRD2 expression in the striatum also exhibited dose dependency and statistically significant decreases were seen in the high-dose group, except in the striatum at bregma level - 1.34. These findings suggest that DR in the caudal striatum is more resistant to the effects of Al exposure than DR in the cortex or rostral striatum. In addition, our results suggest that disturbance of dopaminergic neurotransmission mediated by DRD1 and/or DRD2 may be involved in the pathogenesis of Al neurotoxicity.Human & Experimental Toxicology (2007) 26, 741 —746
Alteration of estrogen-regulated gene expression in human cells induced by the agricultural and horticultural herbicide glyphosate: Hokanson, R. ;Fudge, R. ;Chowdhary, R. ;Busbee, D.
doi: 10.1177/0960327107083453pmid: 17984146
Gene expression is altered in mammalian cells (MCF-7 cells), by exposure to a variety of chemicals that mimic steroid hormones or interact with endocrine receptors or their co-factors. Among those populations chronically exposed to these endocrine disruptive chemicals are persons, and their families, who are employed in agriculture or horticulture, or who use agricultural/horticultural chemicals. Among the chemicals most commonly used, both commercially and in the home, is the herbicide glyphosate. Although glyphosate is commonly considered to be relatively non-toxic, we utilized in vitro DNA microarray analysis of this chemical to evaluate its capacity to alter the expression of a variety of genes in human cells. We selected a group of genes, determined by DNA microarray analysis to be dysregulated, and used quantitative real-time PCR to corroborate their altered states of expression. We discussed the reported function of those genes, with emphasis on altered physiological states that are capable of initiating adverse health effects that might be anticipated if gene expression were significantly altered in either adults or embryos exposed in utero.Human & Experimental Toxicology (2007) 26,747—752
Pattern of acute poisoning in Tehran-Iran in 2003: Shadnia, Shahin ;Esmaily, Hadi ;Sasanian, Ghazal ;Pajoumand, Abdolkarim ;Hassanian-Moghaddam, Hosein ;Abdollahi, Mohammad
doi: 10.1177/0960327107083017pmid: 17984147
To characterize the poisoning cases admitted to the Loghman-Hakim Hospital Poison Center (a teaching reference hospital of poisoning) in Tehran, Iran. All admitted acutely poisoned patients from January to December 2003 were evaluated retrospectively. Information of socio-demographic characteristics, agents and cause of poisoning, and the mortality rate were collected from medical records of the hospital. During this period, 24 179 cases were referred to the emergency department that 10 206 of them were admitted. Of the admitted cases, 51% were male and 49% female. The majority (38%) of cases were in the age range of 21—30 years. Most (79%) of poisonings were intentional and 21% were unintentional. The most important agents of acute poisoning were drugs (69.13%) especially sedative-hypnotics followed by opioids (12.34%) and pesticides especially organophosphates (OPs) (6.21%). The mortality rate was 1.3% (318 patients). Death was mostly occurred by opioids (41.54%), followed by drugs (28%) and pesticides especially OPs (12%). The prevention and treatment of poisoning due to opioids, pesticides specially OPs and sedative-hypnotics drugs should merit high priority in the health care of the indigenous population of Tehran.Human & Experimental Toxicology (2007) 26, 753—756