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Effect of gamma-hexachlorocyclohexane and its isomers on proto-oncogene c-fos expression in brain
M Vendrell1, J M Tusell, J Serratosa
1Dept. de Farmacologia i Toxicologia, CID-CSIC, Barcelona, Spain.
Abstract:
By means of in situ hybridization, the induction of proto-oncogene c-fos in rat brain after administration of several convulsants has been studied. The organochlorine insecticide gamma-hexachlorocyclohexane (lindane) has been shown to induce c-fos expression in a dose dependent manner. 30 mg/kg of lindane increased c-fos expression in cortical and hippocampal areas. The two non convulsant isomers of lindane, alpha- and delta-HCH, were not able to induce the expression of the proto-oncogene, but blocked that elicited by lindane. Pentylenetetrazole (PTZ) and picrotoxin (PTX), a known GABAA-receptor antagonist, have also been considered. Both of them were able to induce c-fos, although the pattern of expression was not the same in each case. alpha- and delta-HCH, were administered prior to the mentioned toxicants, affecting the proto-oncogene expression in different ways. We propose here that the distribution of c-fos mRNA after different treatments can be used as a marker of neurotoxic action.
Insights
This study shows that the insecticide lindane and convulsants like PTZ and PTX can increase c-fos gene expression in rat brains. This c-fos mRNA distribution may serve as a marker for neurotoxic effects.
Area of Science:
- Neuroscience
- Toxicology
- Molecular Biology
Background:
- Proto-oncogene c-fos expression is a marker for neuronal activity.
- Organochlorine insecticides and convulsants can affect brain function.
- Understanding neurotoxic mechanisms is crucial for public health.
Purpose of the Study:
- To investigate the induction of c-fos proto-oncogene expression in the rat brain by various convulsants.
- To determine if c-fos mRNA distribution can serve as a marker for neurotoxic action.
- To examine the effects of lindane isomers and GABAA-receptor antagonists on c-fos expression.
Main Methods:
- In situ hybridization was used to detect c-fos mRNA in rat brain tissue.
- Administration of gamma-hexachlorocyclohexane (lindane), alpha-HCH, delta-HCH, pentylenetetrazole (PTZ), and picrotoxin (PTX).
- Dose-dependent effects of lindane on c-fos expression were analyzed.
Main Results:
- Lindane induced c-fos expression in a dose-dependent manner, particularly in cortical and hippocampal areas.
- Non-convulsant lindane isomers (alpha- and delta-HCH) did not induce c-fos but blocked lindane-induced expression.
- PTZ and PTX induced c-fos expression, but with distinct spatial patterns.
Conclusions:
- The distribution of c-fos mRNA following exposure to toxicants can indicate neurotoxic effects.
- Lindane and GABAA-receptor antagonists modulate c-fos expression in the rat brain.
- c-fos mRNA serves as a valuable biomarker for assessing neurotoxicity.