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Lung Tumor Induction by 26-week Dermal Application of 1,2-Dichloroethane in CB6F1-Tg rasH2 Mice.
- Source :
-
Toxicologic pathology [Toxicol Pathol] 2017 Apr; Vol. 45 (3), pp. 427-434. - Publication Year :
- 2017
-
Abstract
- Short-term alternatives to traditional 2-year carcinogenic studies in rodents are being actively pursued. Recently, a 26-week short-term carcinogenicity study using CB6F1-Tg rasH2@Jcl (rasH2) mice has become a worldwide standard for the evaluation of chemical carcinogenesis. However, an acceptable short-term carcinogenic study model for dermally applied products is still lacking. To investigate the suitability of using the rasH2 mouse to test carcinogenic potential, 1,2-dichloroethane (1,2-DCE) was dermally applied to rasH2 mice: 1,2-DCE is a known carcinogen that causes lung bronchiolo-alveolar adenomas and adenocarcinomas when administered topically, orally, or by inhalation exposure; 1,2-DCE at a dose level of 126 mg/mouse in 200 μl acetone or acetone alone (vehicle control) was applied to the dorsal skin of 10 mice of each sex 3 times a week for 26 weeks. As a positive control, 10 mice of each sex received a single intraperitoneal injection of 75 mg/kg of N-methyl- N-nitrosourea. Bronchiolo-alveolar adenomas and adenocarcinomas were significantly increased in 1,2-DCE-treated rasH2 mice of both sexes, and bronchiolo-alveolar hyperplasias were significantly increased in female mice. Overall, almost all mice of each sex developed adenomas and/or adenocarcinomas with 100% of female rasH2 mice developing bronchiolo-alveolar adenocarcinomas.
- Subjects :
- Adenocarcinoma genetics
Administration, Cutaneous
Animals
Ethylene Dichlorides administration & dosage
Female
Humans
Lung Neoplasms genetics
Male
Adenocarcinoma chemically induced
Carcinogenicity Tests methods
Ethylene Dichlorides toxicity
Genes, ras genetics
Lung Neoplasms chemically induced
Mice, Transgenic
Subjects
Details
- Language :
- English
- ISSN :
- 1533-1601
- Volume :
- 45
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Toxicologic pathology
- Publication Type :
- Academic Journal
- Accession number :
- 28421967
- Full Text :
- https://doi.org/10.1177/0192623317701003