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Biologic Markers in Reproductive Toxicology (1989) / Chapter Skim
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26. Morphologic, Neurochemical, and Behavioral Responses to Toxic Agents
Pages 281-288

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From page 281...
... EFFECTS OF TIME OF EXPOSURE AND DOSE: IRRADIATION AS A PARADIGM The extensive use of ionizing radiation as an embryotoxic agent has been of paramount importance in the delineation of several important concepts that have particular relevance to current efforts in developmental toxicology. Studies in radiation teratology are unique, in that the physics of ionizing radiation has allowed scientists to produce effects in the embryo directly, with no concern for the moderating influence of the so-called placental barrier.
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From page 282...
... Postponing the initial irradiation to PN 8 and 12 produced selective neu renal deficits (stellate and late forming granule cells in one group, lateforming granule cells in another group) with corresponding selective behavioral effects.
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From page 283...
... Focal x irradiation of the hippocampus, begun immediately after birth, prevents the formation of nearly 85% of the granule cells of the dentate gyrus. The rats were then tested in the same 283 postulated that these, and other, selec tive effects on microneuronal populations can provide the anatomic basis for mini mal brain dysfunction under the influence of a broad spectrum of environmental factors, such as alcohol, lead, and gluco corticoids.
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From page 284...
... Those observations link a class of rela tively easily identified and measurable changes in physical structure with abnor mal CNS development with behavioral defi cits. Both the physical structures and the CNS are ectodermal in origin.
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From page 285...
... MPTP was found to be a specific basal ganglia toxin that damages the same nigrostriatal dopaminergic pathways that are affected in parkinsonism (Kopin and Markey, 1988~. The mechanism of action of MPTP involves uptake into dopaminergic neurons, interaction with oxidases within the neurons, and selective cell killing, possibly by the generation of free-radical oxygen or hydroxyl radicals.
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From page 286...
... Because evoked potentials recorded from the scalp or spinal cord reflect activity in multisynaptic pathways, evoked potentials can provide useful information in assessing sensory transmission from the periphery to the cerebral cortex. Three types of evoked potentials have been recorded: auditory evoked potentials for which the stimuli are generally pure tones or clicks, but can be phonemes or words; visual evoked potentials for which the stimuli are stroboscopic light flashes or checkerboard patterns on computer monitors; and somatosensory evoked potentials for which the stimuli are brief electric impulses delivered to the skin.
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From page 287...
... Decreased vibratory sensitivity is observed in many conditions that involve the central and peripheral nervous systems. Among them are systemic disease, such as diabetes, chronic liver failure, pernicious anemia, peripheral neuropathies, syphilis, spinal-cord lesions, and uremia; exposure to pharmaceuticals, such as isoniazid, phenytoin, vincristine, and glutethimide; and exposure to chemicals, such as acrylamide, arsenic, n-hexane, mercury, and methylbutylketone (Maurissen, 1985~.
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From page 288...
... 288 et al., 1987~. Teachers blind to a sub ject's lead exposure reported a dose dependent increase in nonadaptive classroom behavior, such as distractibility, NEURODEKELOPMENTAL TOXICOLOGY inability to work independently, disorganization, hyperactivity, impulsivity, and inability to follow directions (Needleman et al., 1979~.
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Key Terms

  • granule cells
  • lead exposure
  • blood lead
  • behavioral effects
  • mpa scores

  • nerve conduction
  • toxic agents
  • ionizing radiation
  • granule cell
  • conduction time

  • external granule
  • minor physical
  • cell layer
  • eye defects
  • auditory evoked

  • cell killing
  • produced eye
  • integrative capacity
  • selective behavioral
  • cerebral cortex

  • single function
  • cell death
  • physical anomalies
  • regenerative capacity
  • reds produced

  • urinary excretion
  • lead content
  • motor deficits
  • somatosensory evoked
  • microneuronal populations


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