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Dose-response study of N-nitrosomethyl(2-hydroxypropyl)amine-induced nasal cavity carcinogenesis in rats
K Yamamoto1, A Nakajima, H Eimoto
1Department of Oral and Maxillofacial Surgery, Nara Medical College, Japan.
Abstract:
Dose response to the carcinogenic activity of N-nitrosomethyl(2-hydroxypropyl)amine (MHP) was investigated for the nasal cavity of male Wistar rats. MHP dissolved in 0.9% saline was administered intraperitoneally once a week for 12 weeks at doses of 0, 4.4, 8.8 and 17.6 mg/kg body weight, and all surviving animals were sacrificed 26 weeks after the beginning of the experiment. Hyperplasias, papillomas and squamous cell carcinomas were induced. Hyperplasias could be divided into flat, protruding and downgrowth types and were observed in respiratory and squamous epithelial regions. Papillomas and squamous cell carcinomas developed in the respiratory region, and the incidence of the latter reached 83% in rats which received the highest dose of MHP. These results indicate that MHP shows its carcinogenic activity of the nasal cavity by the development of squamous cell carcinomas.
Insights
N-nitrosomethyl(2-hydroxypropyl)amine (MHP) causes nasal cavity tumors in rats. Higher doses of MHP increased the incidence of squamous cell carcinomas, indicating its carcinogenic potential.
Area of Science:
- Toxicology
- Carcinogenesis
- Oncology
Background:
- N-nitrosomethyl(2-hydroxypropyl)amine (MHP) is a chemical compound with suspected carcinogenic properties.
- Investigating the dose-response relationship of MHP is crucial for understanding its toxicological profile.
Purpose of the Study:
- To evaluate the dose-dependent carcinogenic effects of MHP on the nasal cavity of male Wistar rats.
- To determine the specific types of nasal tumors induced by MHP and their incidence at different dose levels.
Main Methods:
- Male Wistar rats were administered intraperitoneal injections of MHP at doses of 0, 4.4, 8.8, and 17.6 mg/kg body weight weekly for 12 weeks.
- Animals were observed for 26 weeks post-administration, and nasal cavity tissues were examined for hyperplasias, papillomas, and squamous cell carcinomas.
Main Results:
- MHP induced hyperplasias (flat, protruding, downgrowth types) in the respiratory and squamous epithelial regions.
- Papillomas and squamous cell carcinomas were predominantly observed in the respiratory region.
- The incidence of squamous cell carcinomas reached 83% in rats receiving the highest MHP dose.
Conclusions:
- MHP exhibits significant carcinogenic activity in the rat nasal cavity.
- The primary carcinogenic effect of MHP involves the induction of squamous cell carcinomas.
- A clear dose-response relationship exists between MHP exposure and the development of nasal tumors.