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Special Issue "Recent Advances in Environmental Health Research: Health Disparities, Toxicology and Carcinogenesis. Part II"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (30 June 2002)

Published Papers (7 papers)

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Research

Open AccessArticle SELDI-TOF-MS Analysis of Transcriptional Activation Protein Binding to Response Elements Regulating Carcinogenesis Enzymes
Int. J. Mol. Sci. 2002, 3(10), 1027-1038; doi:10.3390/i3101027
Received: 7 June 2002 / Accepted: 31 October 2002 / Published: 31 October 2002
Cited by 3 | PDF Full-text (201 KB) | HTML Full-text | XML Full-text
Abstract
The risk from chemical carcinogens and environmental toxins is dependent on the metabolic balance between bioactivation and detoxification enzymes. Therefore, agents that alter enzyme expression are critical factors in toxicity. Enhancement or suppression of enzyme activities through gene expression is in part [...] Read more.
The risk from chemical carcinogens and environmental toxins is dependent on the metabolic balance between bioactivation and detoxification enzymes. Therefore, agents that alter enzyme expression are critical factors in toxicity. Enhancement or suppression of enzyme activities through gene expression is in part regulated by interactions between specific DNA promoter response elements and specific transcription proteins. DNA-protein interactions are dependent upon translocation of proteins from the cytoplasm to the nucleus and the affinity of proteins for binding to transcription promoter sequences. A key factor in both processes is the intracellular redox state, which influences protein-protein interactions and protein-DNA binding and can be altered by exposure to electrophiles, antioxidants and oxidative stress. Oxidative stress levels can be readily detected by measurable effects on the intracellular glutathione (GSH):glutathione disulfide redox potential, the major intracellularredox buffer. Alterations in the GSH redox pool can directly affect enzyme activity by altering disulfide bonds in the transcription factors regulating enzyme expression. These may affect: 1) specific DNA-protein and protein-protein interactions, 2) cyst(e)ine redox state within transcriptional proteins and 3) translocation of transcription proteins from cytoplasmic to nuclear compartments within the cell. The studies reported here are designed to investigate the relative changes in enzyme expression in response to cellular redox potential changes using the new proteomics technology of surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI). Treatment of HeLa and HT29 human cell lines to increase the expression of enzymes that are upregulated by oxidative stress was used as a model system to determine the efficacy of the SELDI technology in measuring changes in transcriptional protein binding to transcriptional response elements. An important goal is to determine whether the SELDI will allow simultaneous studies of multiple transcriptional protein-DNA interactions in response to controlled oxidative stress. This will provide a better understanding of the effect of electrophilic carcinogens and oxidants on the balance between activation and detoxification mechanisms in chemical carcinogenesis. Full article
Open AccessArticle Pilot Study: A Non-Invasive Urine Test for Potential Prostate Abnormalities
Int. J. Mol. Sci. 2002, 3(10), 1039-1047; doi:10.3390/i3101039
Received: 7 June 2002 / Accepted: 31 October 2002 / Published: 31 October 2002
Cited by 1 | PDF Full-text (213 KB) | HTML Full-text | XML Full-text
Abstract
Currently, serum is used more often than urine to detect prostate specific antigen (PSA). The need for a non-invasive test yielding similar results led us to develop a urine test that uses solar irradiated water as a reactant species. To develop this [...] Read more.
Currently, serum is used more often than urine to detect prostate specific antigen (PSA). The need for a non-invasive test yielding similar results led us to develop a urine test that uses solar irradiated water as a reactant species. To develop this technology, seven reagents plus one control were produced by exposure of water for 40 days in sunlight to the colors of the visible spectrum through colored cellophane, control being an unwrapped bottle of sterile water. Patients (127) were examined for serum PSA and the urine was tested using the above reagents. A positive urine test was observed with yellow-filtered irradiated water which absorbed at 454nm. Twenty-five of the 45 patients with positive results for the urine test had PSA levels of 0.21-4.0 ng/ml. Thus, this pilot study describes a non-invasive urine test mainly positive in patients with PSA 0.21-4.0 ng/ml. Full article
Open AccessArticle Effect of Dissolved Humic Substances on the Photochemical Degradation Rate of 1-Aminopyrene and Atrazine
Int. J. Mol. Sci. 2002, 3(10), 1048-1057; doi:10.3390/i3101048
Received: 7 June 2002 / Accepted: 1 September 2002 / Published: 31 October 2002
Cited by 17 | PDF Full-text (185 KB) | HTML Full-text | XML Full-text
Abstract
Humic substances (HS) are ubiquitous in the environment, and can act as photosensitizers in the redox reactions of some photochemical processes. The influence of HS in these reactions varies with the HS type and concentration. The total organic carbon content (TOC) of [...] Read more.
Humic substances (HS) are ubiquitous in the environment, and can act as photosensitizers in the redox reactions of some photochemical processes. The influence of HS in these reactions varies with the HS type and concentration. The total organic carbon content (TOC) of some commercial HS (such as soil and river humic acid, and fulvic acid) was studied. 1-Aminopyrene (1-AP) and 1-hydoxypyrene (1-HP) are carcinogenic and slightly water-soluble polycyclic aromatic hydrocarbons (PAH). The impact of PAH on natural environment is related to their photolysis rates and photoproducts; therefore, it is of interest to study the photolysis of these compounds. Our previous study showed that the photolysis rate of 1-HP was inhibited by HS. In this study, photolysis of 1-AP was conducted with pure water, natural river water, and pure water containing commercial HS. It was found that the photolysis rate of 1-AP can be inhibited or enhanced by HS, depending on the type and concentration. The first order photolysis rate constant of 1-AP (10 μM) in phosphate buffer (pH 7.0, 1 mM) containing a humic acid (20-80 ppm) was enhanced by up to 5 folds. With a fulvic acid (20-80 ppm), it was enhanced by about 2 folds. With a soil humic acid, it was enhanced by about 2 folds at the concentration of 20 ppm and was inhibited by up to 4 folds at the concentration of 80 ppm. Atrazine (2-chloro-4-ethylamine-6-isopropylamino-s-triazine) is a widely used herbicide. It is toxic, often bioaccumulative and persistent. In this study, the effect of HS on the photochemical fate of atrazine was also studied. The results showed that photolysis of atrazine can be enhanced by humic acid, depending on the type and concentration of humic acid. The fulvic acid has no effect on its photolysis within 10 days. Full article
Open AccessArticle Functionally-Impaired HIV-1 Nef Alleles from a Mother-Child Transmission Pair
Int. J. Mol. Sci. 2002, 3(10), 1058-1072; doi:10.3390/i3101058
Received: 7 June 2002 / Accepted: 31 October 2002 / Published: 31 October 2002
Cited by 1 | PDF Full-text (423 KB) | HTML Full-text | XML Full-text
Abstract
Unusual HIV-1 nef alleles were isolated from a woman and her vertically infected child. Both patients eventually progressed to develop AIDS. The child died at age 6.5 years, while the mother is currently alive, 13 years since her diagnosis with HIV-1. Predicted [...] Read more.
Unusual HIV-1 nef alleles were isolated from a woman and her vertically infected child. Both patients eventually progressed to develop AIDS. The child died at age 6.5 years, while the mother is currently alive, 13 years since her diagnosis with HIV-1. Predicted amino acid sequences of both mother and child Nefs diverged from the HIV-1 clade B consensus. In particular, they exhibited two separate 5-amino acid deletions bracketing a Cterminal dileucine regulatory motif and Trp-Gly mutations at the site for cleavage by the HIV-1 protease. The child’s Nef showed a modest ability to enhance HIV-1 infectivity in MAGI cells, whereas the mother’s Nef did not alter HIV-1 infectivity in the assay. Both Nefs were partially functional for CD4 down-regulation. The child’s Nef was fully functional for MHC-1 down-regulation, while the maternal Nef was non-functional. To our knowledge this study is the first to describe a functional divergence between Nef alleles in a case of mother-to-child HIV-1 transmission. Full article
Open AccessArticle Methyl Parathion Masks Withdrawal from Physical Dependence on Morphine
Int. J. Mol. Sci. 2002, 3(10), 1073-1081; doi:10.3390/i3101073
Received: 7 June 2002 / Accepted: 31 October 2002 / Published: 31 October 2002
Cited by 3 | PDF Full-text (186 KB) | HTML Full-text | XML Full-text
Abstract
The cholinergic system has been proposed to participate in the development of dependence on opioids. The present study examined effects of dermal pretreatment with methyl parathion (MP), an acetylcholinesterase inhibitor, on the development of physical dependence on morphine. Opioid dependence was induced [...] Read more.
The cholinergic system has been proposed to participate in the development of dependence on opioids. The present study examined effects of dermal pretreatment with methyl parathion (MP), an acetylcholinesterase inhibitor, on the development of physical dependence on morphine. Opioid dependence was induced by continuous intracerebroventricular (i.c.v.) infusion of morphine (26 nmol/μl/h) for 3 days in adult male Sprague-Dawley rats. Each rat received two doses of MP, 12.5 mg/kg, dermally, initially, 3 days prior to initiation of i.c.v. morphine infusion and again on the first day of infusion. Withdrawal was precipitated after 3 days of infusion by administering an opioid antagonist, naloxone (48 nmol/5 μl, i.c.v.). Twelve of 23 MP-treated rats exhibited signs of acetylcholinesterase inhibitor intoxication (mild tremors) and showed reduced spontaneous locomotor activity (tested by an open field test), prior to naloxone. The brain cholinesterase activity in these 12 rats was 13% of levels in control rats. Eleven rats that did not show toxic signs, exhibited cholinesterase activities that were 20% of control (not significant versus toxic group). The group that showed signs of MP intoxication exhibited a significantly lower incidence of opioid withdrawal jumping, rearing and wet dog shakes compared with the non-toxic group. No differences between quantal withdrawal signs (ptosis, penis-licking, and vocalization) were noted between the two groups. The results suggest that toxic inhibition of acetylcholinesterase non-specifically reduces locomotor activity and may obscure certain behavioral signs of withdrawal from opioid dependence. This indicates that caution should be used in interpreting a direct involvement of acetylcholinesterase inhibition in preventing opioid dependence. Full article
Open AccessArticle Health Risk Assessment of Pesticide Usage in Menia El-Kamh Province of Sharkia Governorate in Egypt
Int. J. Mol. Sci. 2002, 3(10), 1082-1094; doi:10.3390/i3101082
Received: 7 June 2002 / Accepted: 31 October 2002 / Published: 31 October 2002
Cited by 9 | PDF Full-text (177 KB) | HTML Full-text | XML Full-text
Abstract
Menia El-Kamh province of the Sharkia Governorate constitutes one of the largest agricultural areas in Egypt. About 88% of the nearly 472,000 people living in this province rely on agricultural activities for subsistence. Several pesticides including organochloride, organophosphorus, carbamate, and pyrethroid insecticides, [...] Read more.
Menia El-Kamh province of the Sharkia Governorate constitutes one of the largest agricultural areas in Egypt. About 88% of the nearly 472,000 people living in this province rely on agricultural activities for subsistence. Several pesticides including organochloride, organophosphorus, carbamate, and pyrethroid insecticides, fungicides, and herbicides are commonly used in citrus, vegetable and other crop-growing areas to increase agricultural productivity. However, their use has also been associated with several cases of pesticide poisoning. In this research, we conducted a field survey to assess the knowledge, attitudes, and practices of the farmer’s community regarding the safe use of pesticides. We also evaluated the residual concentrations of selected pesticides in water, soil, milk, fish, and orange samples, and estimated the potential health risks associated with the exposure to these pesticides. Data obtained from the field survey indicate that more than 95% of farm workers do not practice safety precautions during pesticide formulation and application; leading to a considerable prevalence of pesticide-related illnesses in this agricultural community. Pesticide residues in various environmental samples varied greatly; from below detection levels (3-5 ng) to as high as 325 ppb depending on the matrix of interest, and the specific pesticide of concern. The analysis of health risk estimates indicated that chlorpyrifos, DDT, dimethoate, methomyl, and larvin did not pose a direct hazard to human health, although present in water, milk, orange, and/or fish. However, aldicarb, and carbosulfan levels exceeded the reference doses, indicating a great potential for systemic toxicity, especially in children who are considered to be the most vulnerable population subgroup. The upper-bound values of cancer risk from DDT exposure were estimated to be about 8 (adults), and 55 (children) excess cancers in a population of one million. Full article
Open AccessArticle The Influence of Environmental Temperatures on Neurotoxicity Induced by Methamphetamine in Male Rats
Int. J. Mol. Sci. 2002, 3(10), 1095-1104; doi:10.3390/i3101095
Received: 7 June 2002 / Accepted: 1 September 2002 / Published: 31 October 2002
PDF Full-text (214 KB) | HTML Full-text | XML Full-text
Abstract
Methamphetamine (MAMPH) increases core body temperature at room temperature and decreases it in the cold room. MAMPH at doses ≥ 5.0 mg/kg also induces neural toxicity at room temperature, but not in the cold room. We hypothesized that the neural toxicity of [...] Read more.
Methamphetamine (MAMPH) increases core body temperature at room temperature and decreases it in the cold room. MAMPH at doses ≥ 5.0 mg/kg also induces neural toxicity at room temperature, but not in the cold room. We hypothesized that the neural toxicity of the MAMPH is heat related. Thus, the objectives of these experiments were to investigate the dynamics of heat dissipation and conservation at various ambient temperatures. Forty male Sprague-Dawley rats were divided into four equal groups. Groups 1, 2 and 3 were injected intraperitoneally (i.p.) with saline and one hour later with an equivolume of MAMPH in doses of 2.5, 5.0, or 7.5 mg/kg bwt. Group four was injected with saline/saline. Core body (Tc) and tail skin (Ts) temperatures were recorded with thermistors (YSI series 700) at room temperature (21 ± 1°C) or in a cold room (7 ± 0.5°C) every five minutes for four hours. Tc was used as an index for total body heat, and Ts was used as an index for blood flow to the tail (a measure of heat dissipation /conservation) at various times during the experiment. Analysis of the data (ANOVA and post-hoc) showed that MAMPH at doses of 5.0 and 7.5 mg/kg bwt increased the Tc at room temperature, and decreased the Tc at doses of 2.5, 5.0 and 7.5 mg/kg bwt in the cold room in a dose dependent manner. Analysis of the tail effector mechanism for heat dissipation at room temperature, and for heat conservation in the cold room, demonstrated that Ts does not follow Tc at room temperature, but follows Tc in the cold room. In the cold room, MAMPH treated animals decreased Ts, or probably vasoconstricted the tail as the Tc falls. In contrast, at room temperature, although MAMPH raised the Tc of the animals, there was no evidence for a change in Ts, or no tail vasodilatation. Based on these data, we suggest that MAMPH (i.p.) impair heat dissipation, but not heat conservation. Hence, the accumulated heat in neural tissue may account, in part, for the reported neural toxicity of MAMPH. Full article

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