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Toxicology in the Use, Misuse, and Abuse of Food, Drugs, and Chemicals - Proceedings of the European Society of Toxicology Meeting, held in Tel Aviv, March 21-24, 1982 (Paperback, Softcover reprint of the original 1st ed. 1983)
P.L Chambers, S Gitter, C. M Chambers
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R3,027
Discovery Miles 30 270
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Ships in 10 - 15 working days
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Many chemotherapeutic agents introduced for use in humans are
carcinogenic in laboratory animals (Conklin et al. 1965; Shimkin et
al. 1966; Griswold et al. 1968; Harris 1976). However, initially
their beneficial effect in disseminated cancer was of such short
duration that the inevitable death of the patient from his primary
disease precluded any clinical manifestation of the carcinogenic
potential. During the last decade, chemotherapy has radically
changed the outlook for many patients with cancer. Combinations of
drugs, administered as the primary treatment, have resulted in high
rates of cure in patients with disseminated malignancies, such as
stage IV Hodgkin's disease or childhood acute lymphocytic leukemia.
In other disseminated forms of neoplasia, induction of a remission,
a substantial palliation and a prolongation of survival have been
achieved. In many instances of localised disease, where surgery
with or without radiotherapy are the primary form of treatment,
anticancer drugs have been used with success as adjuvant therapy
for distant microscopic disease. With these spectacular
achievements, secondary malignancies, in particular acute
non-lymphocytic leukemia (ANLL), has become of major concern.
Incidence Acute leukemia is the most frequent form of secondary
neoplasia in patients treated for cancer (Penn 1981). In one large
series, 5. 9% of all ANLL could be attributed to previous
chemotherapy (Kapadia et al. 1980).
Nervous system is in the most cases a likely target for the
untoward effects of chemicals. The harmful consequences affect
primarily the individual but may also considerably strain the whole
society. The consumption of ethanol is a glaring example (National
Institute on Alcohol Abuse and Alcoholism 1978). As ethanol, many
organic liquids have similar immediate effects on the nervous
system. The rapidity of the response suggests the involvement of
the neuronal communication. The nervous system is also vulnerable
to the depletion of oxygen, another common cause for the rapid
deterioration of the brain function. It is quite impossible to list
all the effects produced by the very large number of the individual
chemicals. It would be more fruitful to try to understand the
characteristics of the nervous system and the biochemical toxic
mechanisms in the evaluation of the neurotoxicity of chemicals.
Transfer of Xenobiotics in the Brain The adult central nervous
system displays a functional barrier toward the blood-borne
chemicals so that water-soluble compounds with an approximate
molecular weight above 100 are largely prevented from directly
entering the brain (Bradbury 1979). The functional barrier has
morphological features typical to it and has a very close
association of adjacent capillary cells separated by clefts of 12 A
wide (Jacobs 1978). The nervous system capillaries are enveloped by
glial cell tongues, and these pericytes contain contractile
elements (Le Beux and Willemot 1978a, b) so that the capillaries
can be constricted.
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