Related Experiment Videos
Target organ specificity of cell proliferation induced by various carcinogens
Y Yoshida1, M Tatematsu, K Takaba
1First Department of Pathology, Nagoya City University Medical School, Japan.
Abstract:
The target organ specificities of cell proliferation and histopathological lesion induction by 5 carcinogens having different target organs were evaluated using a multiorgan carcinogenesis bioassay. In Group 1, male F-344 rats aged 6 wk were sequentially treated with N-diethylnitrosamine (DEN, single 100-mg/kg ip injection, week 0), N-methyl-N-nitrosourea (MNU, 4 20-mg/kg ip injections, weeks 0-2), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN, 0.05% in drinking water, weeks 0-2), N,N'-dimethylhydrazine (DMH, 4 40-mg/kg sc injections, weeks 2-4), and dihydroxy-di-N-propylnitrosamine (DHPN, 0.1% in drinking water, weeks 2-4) during the first 4 wk. In Groups 2-6, rats were treated with only one of the above initiators, applied as in Group 1. Group 7 served as the no-treatment control. Bromouracil deoxyriboside (BUdR) labeling indices (LI) were counted in various organs at weeks 2 and 4. Numbers and areas of glutathione S-transferase placental form positive (GST-P+) liver foci were measured at weeks 2, 4, and 28. Preneoplastic or neoplastic lesion development was assessed at week 28. With regard to specific elevation of cell proliferation in target organs, BUdR LIs in the urinary bladder, liver, and colon were, respectively, increased in the BBN alone, DEN alone, and DMH alone treated groups as well as in Group 1. However, LIs of thyroid, lung, and kidney were also elevated by several carcinogens not including these organs in their carcinogenic target specificity. On the other hand, morphological lesions and GST-P+ foci were limited to Group 1 and the target organs of the corresponding carcinogen-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study investigated how five carcinogens affect cell proliferation and lesion development in rats. While some carcinogens specifically increased cell proliferation in target organs, others caused broader effects, with lesions primarily appearing in expected target sites.
Area of Science:
- Toxicology and Carcinogenesis
- Experimental Pathology
- Biomarker Discovery
Background:
- Understanding target organ specificity of carcinogens is crucial for risk assessment.
- Multiorgan carcinogenesis bioassays provide insights into complex toxicological mechanisms.
- Cell proliferation and preneoplastic lesions are key indicators of carcinogenic activity.
Purpose of the Study:
- To evaluate target organ specificities of cell proliferation and histopathological lesion induction by five distinct carcinogens.
- To compare the effects of sequential multi-carcinogen exposure versus single carcinogen exposure in rats.
- To correlate early cell proliferation markers with later preneoplastic and neoplastic lesion development.
Main Methods:
- A multiorgan carcinogenesis bioassay was conducted on male F-344 rats.
- Sequential administration of five carcinogens (DEN, MNU, BBN, DMH, DHPN) or single carcinogen treatments were employed.
- Bromouracil deoxyriboside (BUdR) labeling indices (LI) and glutathione S-transferase placental form positive (GST-P+) foci were quantified; lesions were assessed at 28 weeks.
Main Results:
- BUdR LIs specifically increased in target organs (urinary bladder, liver, colon) for BBN, DEN, and DMH, respectively, and in the multi-carcinogen group.
- Some carcinogens elevated LIs in non-target organs (thyroid, lung, kidney).
- Morphological lesions and GST-P+ foci were predominantly observed in the target organs of the respective carcinogen-treated groups and the multi-carcinogen group.
Conclusions:
- Carcinogen-induced cell proliferation can occur in both target and non-target organs.
- Histopathological lesions and GST-P+ foci demonstrate higher specificity for target organs.
- This study highlights the differential effects of carcinogens on cell proliferation versus lesion development.