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Strain differences in tissue repair response to 1,2-dichlorobenzene
S G Kulkarni1, H Duong, R Gomila
1Division of Toxicology, College of Pharmacy and Health Sciences, Northeast Louisiana University, Monroe 71209-0470, USA.
Archives of Toxicology
|January 1, 1996
Summary
Fischer 344 rats show higher liver injury from 1,2-dichlorobenzene but compensate with faster tissue repair, equalizing survival outcomes compared to Sprague Dawley rats. This highlights the critical role of regenerative capacity in mitigating chemical toxicity.
Area of Science:
- Toxicology
- Hepatology
- Comparative Pathology
Background:
- Fischer 344 (F344) rats exhibit significantly higher sensitivity to 1,2-dichlorobenzene (o-DCB) induced hepatotoxicity compared to Sprague Dawley (S-D) rats.
- Despite reported sensitivity differences, Lethal Dose 50 (LD50) studies revealed no significant difference in o-DCB lethality between F344 and S-D rat strains.
- Tissue repair mechanisms are crucial for survival following toxic chemical exposure, suggesting a potential role in explaining differential toxicity outcomes.
Purpose of the Study:
- To investigate whether differential rates of cell division and tissue repair explain the lack of difference in LD50 between F344 and S-D rats, despite greater hepatotoxic injury in F344 rats.
- To compare liver injury and regeneration dynamics in F344 and S-D rats following exposure to varying doses of o-DCB.
Main Methods:
- Male F344 and S-D rats were administered o-DCB (0.2, 0.6, 1.2 ml/kg, i.p.) and monitored for liver injury and tissue repair markers over time.
- Liver injury was assessed using plasma alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities, and liver histopathology.
- Hepatocellular regeneration was quantified via 3H-thymidine incorporation into hepatonuclear DNA and proliferating cell nuclear antigen (PCNA) assays.
Main Results:
- F344 rats exhibited higher plasma ALT elevations and, at lower doses (0.2 ml/kg), greater SDH elevation, indicating more severe liver injury.
- Prompt and significantly higher hepatocellular regeneration, indicated by 3H-thymidine incorporation and PCNA, was observed in F344 rats at doses of 0.2 and 0.6 ml o-DCB/kg.
- Higher hepatic glycogen depletion in F344 rats correlated with stimulated tissue repair, but higher o-DCB doses (1.2 ml/kg) led to delayed and diminished regeneration in this strain.
Conclusions:
- Fischer 344 rats possess a significantly higher capacity for liver tissue repair, enabling them to overcome greater o-DCB-induced hepatotoxicity compared to Sprague Dawley rats.
- Differential tissue repair rates play a critical role in equalizing the ultimate survival outcomes between F344 and S-D rats exposed to o-DCB.
- The study underscores the importance of regenerative processes in determining toxicological outcomes and strain-specific responses to chemical exposure.