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Abstracts of
Current Literature in Toxicology
Banu BS., Danadevi K., Jamil K., Ahuja YR., Rao KV., Ishaq M
(Department of Genetics, Osmania University, Hyderabad, Andhra
Pradesh, India): In vivo genotoxic effect of arsenic trioxide in
mice using comet assay. Toxicology, 162(3), 2001, 171-177. [30
Ref]
Although arsenic has been the subject of toxicological research, acute
in vivo genotoxic studies using relevant 33 водопада Сочи animals models and uniform
methodology are lacking. Hence, the present study aims to study DNA
damage caused by arsenic trioxide in mice in in vivo using alkaline
single cell gel electrophoresis (Comet) assay. Mice were administered
orally 0, 0.13, 0.27, 0.54, 1.08, 2.15, 4.3 and 6.45 mg/kg body weight
of arsenic trioxide dissolved in distilled water. The samples of whole
blood were collected at 24, 48, 72 h, first and second week
post-treatment and the assay was carried out to determine DNA damage
as represented by comet tail-length. All the doses induced significant
increase in comet tail-length at 24 h post-treatment (P<0.05) showing
a clear dose dependent increase from 0.13 to 2.15 mg/kg b.wt. and a
dose dependent decrease in higher doses (4.3-6.45 mg/kg b.wt.). At 48
h post-treatment, all the doses showed a significant increase (P<0.05)
in comet tail-length when compared to 24 h post-treatment. A gradual
decrease in the comet tail-length was observed for all the doses from
72 h post-treatment onwards indicating a gradual repair in DNA damage.
This indicates a non-linear dose and time response between DNA damage
and different doses of arsenic trioxide at different time-intervals. A
significant increase in comet tail-length at all the doses clearly
gives evidence that arsenic trioxide cause DNA damage effectively. The
study indicates that the alkaline comet assay is a reliable and
effective method to detect DNA damage caused by metals.
Campbell A., Hamai D., Bondy SC* (Department of Community and
Environmental Medicine, Center for Occupational and Environmental
Health, University of California, Irvine, CA 92697-1820, USA):
Differential toxicity of aluminum salts in human cell lines of neural
origin: implications for neuro-degeneration. Neurotoxicol, 22(1),
2001, 63-71. [28 Ref]
Aluminum is highly oxophilic and its minerals are sually found
surrouded by six-oxygen atoms. A role for the metal has been
established in dialysis encephalopathy and Al-induced osteomalacia.
The metal has been implicated in Alzheimer's disease but the issue is
at present controversial. Human cell lines of neural origin were
utilized to study the effect of lipophilic aluminum acetylacetonate
and non-lipophilic aluminum sulfate on cell proliferation and
viability. Although analysis of Al species in the cell culture media
demonstrated that there are positively charged Al species present in
solutions prepared with both Al salts, only the aluminum
acetylacetonate salt caused changes in cell proliferation and
viability. Therefore, the lipophilic nature of the organic Al salt is
a critical determinant of toxicity. The effect of aluminum
acetylacetonate was dose-dependent and time-dependent. Neuroblastoma
(SK-N-SH) cells were more susceptible to decreased cell proliferation
although the lipophilic Al salt was more toxic to the glioblastoma
(T98G) cells. While the toxicity of aluminum acetylacetonate was
inhibited in the T98G cells by the addition of phosphate, the same
treatment did not reverse cell death in the SK-N-SH cells. Thus, the
mechanism of Al toxicity appears to be different in the two cell
lines. It is possible that the principal neurotoxic target of the
metal is glial and when these cells are in a compromised state, this
may secondarily impact the neuronal population and thus eventually
lead to neuro-degeneration.
Won YK., Liu J., Olivier K., Zheng Q., Pope CN (College of Veterinary
Medicine, Oklahoma State University, 264 McElroy Hall, Stillwater, OK
74078, USA): Age-related effects of chlorpyrifos on acetylcholine
release in rat brain. Neurotoxicol, 22(1), 2001, 39-48. [56 Ref]
Chlorpyrifos (CPF) is an organophosphorus insecticide that elicits
toxicity through inhibition of acetylcholinesterase (AChE). Young
animals are markedly more sensitive than adults to the acute toxicity
of CPF. We evaluated acetylcholine (ACh) release and its muscarinic
receptor-mediated regulation (i.e. muscarinic autoreceptor function,
MAF) during maturation as a possible contributing factor to
age-related differences in sensitivity. Cortical and striatal slices
were prelabeled with [3H]choline chloride, superfused in the presence
or absence of the anticholinesterase physostigmine (PHY, 20 uM) and
stimulated twice (S1 and S2} with a high concentration of potassium
chloride (20 mM). Depolarization-stimulated ACh release (DSAR) was
lowest in neonatal intermediate in juvenile and markedly higher in
adult tissues. MAF was not detectable in tissue from neonatal rats but
was present in juvenile and adult tissues. ACh release and MAF were
studied at 4, 24 and 96 h following oral exposure to CPF (0, 0.5 or
1xLD10). In general, 40-60% and 80-90% maximal AChE inhibition
followed exposure to the respective 0.5 and 1xLD10 dosages. DSAR was
decreased in neonatal cortex 1 day after LD10 exposure but increased
in juvenile striatum 1 day after LD10 treatment. In adults, DSAR was
reduced at 4 and 24 h after exposure, but increased 96 h after CPF
exposure. In juveniles, MAF was reduced in both brain regions at 24h
after 0.5LD10 exposure and at 24 and 96 h after LD10 exposure in
cortex. A later reduction in MAF was noted in adult tissues (i.e. only
at 96h after LD10 treatment). Together, the results suggest that ACh
release dynamics in brain vary markedly during postnatal maturation
and that acute CPF exposure can alter ACh release in an age-related
manner. The functional status of presynaptic processes regulating
neurotransmitter release may contribute to age-related neurotoxicity
elicited by high-dose exposure to chlorpyrifos.
Manzo L., Castoldi AF., Coccini T., Prockop LD (Toxicology Division,
University of Pavia, Foundation IRCCS, Institute of Pavia, Pavia
27100, Italy): Assessing effects of neurotoxic pollutants by
biochemical markers. Environ Res Sec. A, 85(1), 2001, 31-36. [48
Ref]
Nuerotoxins cause biochemical and molecular events which indicate
early stage effects in exposed persons well before or well below the
induction of overt disease. Monitoring these early events may
represent a valid approach to developing markers of neurotoxicity in
individuals exposed to environmental chemicals. In neurotoxicology,
the use of biochemical markers is more problematic compared to other
fields due to the complexity of central nervous system function, the
multistage nature of neurotoxic events, and the inaccessibility of
target tissue. Neverthless, new biochemical assays have been developed
in recent years to assess exposure, subclinical effects, and
susceptibility to neurotoxic disorders. This paper reviews novel
biomarkers of neurotoxicity and discusses perspectives and limitation
of their use in occupational and environmental medicine.
Jelks K., Berger T., Horner C., Miller MG (Department of Environmental
Toxicology, University of California Davis, Davis, CA95616, USA):
a-Chlorohydrin induced changes in sperm fertilizing ability in the
rat: association with diminished sperm ATP levels and motility.
Rep Toxicol, 15(1), 2001, 11-20. [37 Ref]
In the present study, a-chlorohydrin (ACH) (5,10,25,50 and 75 mg/kg.
po) was administered to rats and the effect on sperm ATP levels, sperm
motility, and the ability of sperm to bind and penetrate rat oocytess
were determined. Groups of rats were killed 5 days and 3 h following
treatment. At both time points, sperm from ACH-treated rats (>- 10
mg/kg) had significantly lower levels of ATP when diluted in media
containing glucose. No diminution of ATP was seen in sperm diluted in
phosphate-buffered saline (PBS). Computer analysis of sperm motility
indicated that straight-line velocity (VSL) was the most sensitive
parameter to ACH treatment and was significantly decreased in rat
sperm three hours after ACH exposure (25 mg/kg). A clear drop in
percent penetration (35% vs, 85% in control) of zona-free rat oocytes
by rat sperm of both ACH groups was observed at 10 mg/kg. Higher dose
levels produced no significant further decrease in percent
penetration. Overall, the fertilizing ability of sperm was highly
sensitive to ACH doses that caused minor but significant changes in
sperm ATP levels and no significant changes in motility. These data
are consistent with the spermatozoan's need for an uncompromised
energy supply to maintain its ability to bind and penetrate the oocyte.
Christiani DC., Sharp RR., Collman GW., Suk WA (Occupational Health
Program, Harvard School of Public Health, 665 Huntington Avenue,
Boston, MA 02115, USA): Applying genomic technologies in
environmental health research: Challenges and opportunities. J
Occup Environ Med, 43(6), 2001, 526-532. [20 Ref]
Recent discoveries in molecular biology and genetics have made it
possible for environmental health researchers to examine how genetic
characteristics affect response to environmental exposures.
Understanding such gene-environment interactions offers exciting
possibilities for the prevention and control of environmentally
induced diseases. Despite these potential benefits, the collection and
analysis of genetic information in environmental health research
presents many of the same ethical, legal, and social (ELSI) challenges
found in other types of genetic research. In this article, we describe
a number of ELSI challenges in environmental genomic research and the
apportunities and responsibilities that accompany this research.
Frumkin H., Letz R., Williams PL., Gerr F., Pierce M., Sanders A.,
Elon L., Manning CC., Woods JS., Herzberg VS., Mueller P., Taylor BB
(Department of Environmental and Occupational Health, Rollins School
of Public Health of Emory University, 1518 Clitton Road, Atlanta GA
30322, USA): Health effects of long-term mercury exposure among
chlorakali plant workers. Am J Ind Med, 39(1), 2001, 1-18. [80
Ref]
Inorganic mercury is toxic to the nervous system, kidneys, and
reproductive system. We studied the health effects of mercury exposure
among former employeews of a chloralkali plant that operated from 1955
to 1994 in Georgia. Former plant workers and unexposed workers from
nearby employers were studied. Exposure was assessed with a job-exosure
matrix based on historical measurements and personal records. Health
outcomes were assessed with interviews, physical examinations,
neurological and neurobehavioral testing, renal function testing, and
urinary porphyrin measurements. Exposure-disease association were
assessed with multivariate modeling. Exposed workers reported more
symptoms, and tended toward more physical examination abnormalities,
than unexposed workers. Exposed workers performed worse than unexposed
subjects on some quantitative tests of vibration sense, motor speed
and coordination, and tremor, and on one test of cognitive function.
Few findings remained significant when exposure was modeled as a
continuous variable. Neither renal function nor porphyrin excretion
was associated with mercury exposure. Mercury-exposed chloralkali
plant workers reported more symptoms than unexposed controls, but no
strong associations were demonstrated with neurological or renal
function or with porphyrin excretion.
Singh AK., Varma NK., Ahmad I., Sahay N., Singh RP (Central Mining
Research Institute, Dhanbad, Bihar, India): Environmental health
hazards in coal mines with sapecial reference to radioactivity and its
control-A review. Crit Rev Environ Sci technol, 31(1), 2001,
63-77. [17 Ref]
The development of a country depends very much on the advancement of
its industrialization. However, as a result of mass scale
industrialization, the world's environment is being polluted day by
day and endangering the existence of living beings on Earth. This has
attracted the attention of environmental engineers, medical
practioners, planners, and researchers throughout the world. Attempts
are being made to make air, water, and the atmosphere clean and to
prevent likely hazards arising out of various industrial activities.
In addition, radiation from natural sources is all around us and has
been from the advent of time. It is responsible for the radiation
exposure of most of the population. Coal miners have small
occupational exposures that arise from naturally occurring radioactive
substances under ground. The predominant source of natural radiation
present in coal mines is radon gas. This article describes the origin
of radon, radiological hazard, and an attempt has been made to review
the tatus of the problem likely to be caused by the different
radioactive elements present in Indian coal and coal ash and allied
coal-based industries.
Pande M., Mehta A., Pant BP., Flora SJS (Division of Pharmacology and
Toxicology, Defence Research and Development Establishment, Jhansi
Road, Gwalior 474002, India): Combined administration of a
chelating agent and an antioxidant in the prevention and treatment of
acute lead intoxication in rats. Environ Toxicol Pharmacol, 9(4),
2001, 173-184. [43 Ref]
The administration of chelating agents, meso 2,3-dimercaptosuccinic
acid (DMSA, monoisoamyl DMSA (MiADMSA) either individually or in
combination with an antioxidant, n-acetylcystein (NAC) in the
prevention and treatment of acute lead intoxication in rats, was
investigated. The results suggest that concomitant oral
supplementation of DMSA with lead was most effective in preventing the
inhibition of lead sensitive blood d-aminolevulinic acid dehydratase (ALAD)
activity in blood, elevation of zinc protoporphyrin level and the
alterations in hepatic reduced and oxidized glutathione (GSH and GSSG)
contents. A number of other biochemical variables eitehr remained
insensitve to lead exposure or responded moderately to chelation
treatment. Combined administrations of NAC plus DMSA was most
effective when given during lead exposure to post exposure, followed
by DMSA and MiADMSA alone or NAC plus MiADMSA treatment, in reducing
the accumulation of lead in blood and liver. Administration of NAC
alone was only mildy effective in preventing lead absorption in the
blood and tissues. The results suggest that combined administration of
DMSA and NAC could be a more effective treatment protocol for acute
lead toxicity, keeping in view its beneficial effect on oxidative
injury.
Abu-Qare AW., Abou-Donia MB (Department of Pharmacology and Cancer
Biology, Duke University Medical Center, Durham, North Carolina 27710,
USA): Simultaneous determination of chlorpyrifos, permethrin, and
their metabolites in rat plasma and urine by high-performance liquid
chromatography. J Anal Toxicol, 25(4), 2001, 275-279, 19 Ref.
A
high-performance liquid chromato-graphic (HPLC) method was developed
for the separation and quantification of the insecticide chlorpyrifos
(O,O-diethyl-O[3,5,6-trichloro2-pyridinyl] phosphoro-thioate) its
metabolites chlorpyrifos-oxon (O,O-diethyl O[3,5,6-
trichloro-2-pyridinyl] phosphate) and TCP (3,5,6-trichloro2- pyridinol),
the insecticide permethrin (3-(2,2-dichlro-ethenyl)-2, 2-dimethyl-
cyclopropanecarboxylic acid -(3-phenoxyphenyl) methylester), and
two of its metabolites, in phenoxybenzyl alcohol and m-phenoxybenzoic
acid, in rat plasma and urine. The method is based on using C18
Sep-Pak cartridges for solid-phase extraction and reversed-phase HPLC.
The compounds were separated using a gradient of 1 to 80% acetonitrile
in water (pH 3.2) at a flow rate ranging between 1 and 1.5 mL/min in
period of 17 min and gradient UV detection ranging between 210 and 280
nm. The retention times ranged from 9.3 to 14.5 min. The limits of
detection ranged between 20 and 150 ng/mL, whereas the limits of
quantitation were 150-200 ng/mL. The respective average percentage
recoveries of chlorpyrifos, chlor-pyrifos-oxon, TCP, permethrin, m-phenoxybenzyl
alcohol, and m-phenoxy-benzoic were 78.6±6.4,
72.8±6.8,
84.8±8.0,
79.2±8.4,
80.5±7.2,
and 82.3±7.1
from five spiked plasma samples and 77.5±8.1,
72.8±8.3,
79.9±6.4,
79.1±8.9,
80.5±7.6,
and 81.4±7.8
from urine samples. The relationship between peak areas and
concentration was linear for concentrations between 200 and 2000 ng/ml.
This method was used to analyze these chemicals and metabolites
following dermal administration in rats.
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