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Mammary tumor induction by N-methyl-N-nitrosourea in genetically resistant Copenhagen rats
1Ontario Cancer Institute, Toronto, Canada.
Abstract:
The Copenhagen rat is completely resistant to mammary cancer induction by N-methyl-N-nitrosourea (MNU) when the carcinogen is administered during sexual development, a period when other strains of rats are normally susceptible to mammary gland carcinogenesis. Here we administered 30 mg/kg MNU i.p. to two groups of neonatal (2-3-day-old) Copenhagen rats. One group (group B, 18 animals) received no further treatment, while the other group (group C, 17 animals) received a second dose of 30 mg/kg MNU via the tail vein at 50 days of age. About 30% of the rats in group B and about 70% of those in group C developed mammary carcinomas before they were 1 year of age. About one-half of the tumors in both groups were cribriform adenocarcinomas and one-half were adenosquamous carcinomas. The latter tumor type has not been observed previously in susceptible rat strains. The ability to induce these mammary tumors in the Copenhagen rat suggests that the putative mammary carcinoma suppressor gene is functionally inactive in neonatal animals or is inactivated when these animals are treated with MNU.
Insights
Copenhagen rats, typically resistant to mammary cancer, developed tumors after N-methyl-N-nitrosourea (MNU) exposure. A second MNU dose significantly increased tumor incidence, suggesting a suppressor gene may be inactive or inactivated.
Area of Science:
- Oncology
- Genetics
- Toxicology
Background:
- Copenhagen rats exhibit resistance to mammary cancer induced by N-methyl-N-nitrosourea (MNU).
- This resistance is observed when MNU is administered during sexual development, a period of susceptibility in other rat strains.
Purpose of the Study:
- To investigate mammary cancer induction in Copenhagen rats using MNU.
- To explore the role of a putative mammary carcinoma suppressor gene in this rat strain.
Main Methods:
- Neonatal Copenhagen rats (2-3 days old) received an initial dose of MNU (30 mg/kg).
- One group received a second MNU dose at 50 days of age; a control group did not.
- Tumor development and type were monitored up to 1 year of age.
Main Results:
- Approximately 30% of rats receiving a single MNU dose developed mammary carcinomas.
- Mammary tumor incidence increased to about 70% in rats receiving two MNU doses.
- Tumors included cribriform adenocarcinomas and novel adenosquamous carcinomas.
Conclusions:
- Mammary tumors can be induced in Copenhagen rats, challenging their presumed resistance.
- The findings suggest the mammary carcinoma suppressor gene may be functionally inactive in neonates or inactivated by MNU treatment.