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Partial Lobular Hepatectomy: A Surgical Model for Morphologic Liver Regeneration
Published on: May 31, 2018
Gender differences in the liver micronucleus test in rats with partial hepatectomy
Satoru Itoh1, Chiharu Hattori, Mayumi Nagata
1Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Horikoshi 717, Fukuroi-shi, Shizuoka 437-0065, Japan. itoh.satoru.n5@daiichisankyo.co.jp
Toxicology Letters
|September 18, 2012
Summary
The liver micronucleus test effectively detects genotoxicity in male and female rats. While responses to some inducers varied by sex, male rats generally showed equal or stronger responses, suggesting their use may be sufficient.
Area of Science:
- Toxicology
- Genetics
- Biochemistry
Background:
- The liver micronucleus test is valuable for detecting pro-clastogens.
- Previous studies indicated timing of inducer administration relative to partial hepatectomy is crucial for liver genotoxicity detection.
- A potential gender difference in response to chromosome aberration inducers was observed.
Purpose of the Study:
- To investigate gender-specific responses to structural and numerical chromosome aberration inducers in the rat liver micronucleus test.
- To determine if male rats alone are sufficient for this genotoxicity assay.
Main Methods:
- F344 rats (male and female) were administered structural (diethylnitrosamine, 1,2-dimethylhydrazine) or numerical (colchicine, carbendazim) chromosome aberration inducers.
- Chemicals were given before or after partial hepatectomy.
- Hepatocytes were isolated 4 days post-hepatectomy for micronucleus analysis.
Main Results:
- Diethylnitrosamine and 1,2-dimethylhydrazine induced significant micronucleated hepatocytes in both genders with comparable responses.
- Colchicine and carbendazim resulted in higher frequencies of micronucleated hepatocytes in males compared to females.
- Overall, male rats exhibited equal or stronger responses to chromosome aberration inducers than female rats.
Conclusions:
- The rat liver micronucleus test is a viable method for assessing genotoxicity in both male and female rats.
- Male rats may be sufficient for this test, provided no significant gender-specific toxicological differences are known.
- Further investigation into gender differences may be warranted if existing data suggests otherwise.

