80 BIOLOGICAL EFFECTS OF LOW LEVEL EXPOSURES
injury, leading to massive coagulative hepatic necrosis, is observed.214-16
Likewise, it has been demonstrated experimentally that restoring the tissue
hormesis (Figure 4.7) results in an obtundation of the progressive phase of
injury, permitting the tissue to overcome injury.
The central role of hormetic mechanisms in the final outcome of tissue
injury becomes self-evident from the following lines of experimental evi
dence. Prior exposure to 225 ppm phenobarbital results in the potentiation
of liver injury by the same subtoxic dose of CC1 4 employed in the chlorde-
cone + CC1 4 interaction.16’55 56’85 The quantitative measures of liver injury at
24 hr after the administration of CC1 4 indicate that the tissue injury is either
equivalent to or slightly greater than that seen in chlordecone + CC1 4
interaction.55 Left alone, the animals undergoing the interactive toxicity of
phenobarbital + CC1 4 recover, while those experiencing the chlordecone +
CC1 4 interaction do not.214-16’56 While the enhanced liver injury observed
with the interactive toxicity of phenobarbital + CC1 4 is consistent with the
increased bioactivation of CC14,55 106 recovery from this injury is consistent
Figure 4.7. Scheme illustrating the concept of separating those mechanisms that are
responsible for the infliction of cellular and tissue injury from those that follow
these events. Intoxication mechanisms result in infliction of injury during
Stage I of toxicity. During Stage II of toxicity, tissue hormetic mechanisms are
stimulated in an attempt to overcome injury. If these hormetic mechanisms
are unperturbed, recovery occurs. Interference with these mechanisms
results in uncontrollable progression of injury, much like an unquenched
brushfire progressing to become a forest fire.