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Carcinogenic susceptibility to N-bis(2-hydroxypropyl)nitrosamine (DHPN) in rasH2 mice.

Abstract
To evaluate the susceptibility of rasH2 mice to N-bis(2-hydroxypropyl)nitrosamine (DHPN), a potent carcinogen targeting the lung, liver, thyroid, and kidney, male, 6-week old, rasH2 mice and wild-type littermates (non-Tg mice) were given DHPN in drinking water at 0, 20 or 200 ppm, and 0 or 200 ppm, respectively, for 26 weeks. The experiment using rasH2 mice given 200 ppm DHPN and non-Tg mice given 200 and 0 ppm DHPN was completed at 20 weeks, since mortality in these groups was remarkably increased due to hemangiosarcomas of the liver. Histologically, tumors developed in the lung and liver in both rasH2 and non-Tg mice treated with DHPN. In addition, proliferative lesions were observed in the forestomach, urethra, and excretory duct of salivary glands in rasH2 mice given 200 ppm DHPN. RT-PCR analysis showed no marked difference in expression of mRNAs for the transgene and the endogenous mouse ras gene between the whole lung tissue containing a neoplasm and normal lung tissue. Our results suggest that rasH2 mice are highly susceptible to DHPN, the target organs including the forestomach, salivary gland and urethra, which have not been found to develop tumors in previous long-term carcinogenicity studies of DHPN in rats and mice.
AuthorsMiwa Okamura, Mitsuyoshi Moto, Yoko Kashida, Noboru Machida, Kunitoshi Mitsumori
JournalToxicologic pathology (Toxicol Pathol) 2004 Jul-Aug Vol. 32 Issue 4 Pg. 474-81 ISSN: 0192-6233 [Print] United States
PMID15223773 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Carcinogens
  • Nitrosamines
  • RNA, Messenger
  • diisopropanolnitrosamine
Topics
  • Administration, Oral
  • Animals
  • Carcinogenicity Tests (mortality, veterinary)
  • Carcinogens (administration & dosage, toxicity)
  • Disease Susceptibility (chemically induced, veterinary)
  • Dose-Response Relationship, Drug
  • Genes, ras
  • Hemangiosarcoma (chemically induced, genetics, pathology, veterinary)
  • Humans
  • Liver Neoplasms (chemically induced, genetics, pathology, veterinary)
  • Lung Neoplasms (chemically induced, genetics, pathology, veterinary)
  • Male
  • Mice
  • Mice, Transgenic
  • Nitrosamines (administration & dosage, toxicity)
  • RNA, Messenger (metabolism)
  • Salivary Gland Neoplasms (chemically induced, genetics, pathology, veterinary)
  • Stomach Neoplasms (chemically induced, genetics, veterinary)
  • Survival Analysis
  • Survival Rate
  • Toxicity Tests, Chronic (veterinary)
  • Transgenes
  • Urethral Neoplasms (chemically induced, genetics, pathology, veterinary)

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