Coexistence of different tissue tumourigenesis in an N-methyl-N-nitrosourea-induced mammary carcinoma model: a histopathological report in Sprague-Dawley rats.

N-methyl-N-nitrosourea (MNU), a highly potent carginogen, is widely used to generate mammary tumours in murine species. In a model of MNU-induced mammary carcinogenesis using immature female Sprague-Dawley rats, large mammary tumours (largest dimension > or =0.5 cm) were obtained within a very short period of time. In addition, in the rats bearing MNU-induced mammary carcinomas, there were a number of tumours whose origins were not from mammary tissue but from several different tissues and from mammary non-epithelial tissue. The tumours were of mesenchymal or epithelial origin and they were located in the inguinal region. These tumours were diagnosed as fibroadenoma, combined tubular adenoma and fibroadenoma, hyperkeratotic papilloma, keratinous cyst and malignant peripheral nerve sheath tumour (MPNST) with smooth muscle differentiation. The occurrence of these other tumours in addition to the development of the mammary carcinomas may be attributed to a direct local effect of the intraperitoneal administration of MNU during the sexual development of the immature rats. In the MNU-induced mammary tumour model, coexistence of tumourigenesis in various non-mammary tissues should be considered an important factor that may interfere with experimental procedures and results and also the quality of life of the tumour-bearing animals.

Salmonella typhimurium aroB mutants are attentuated in BALB/c mice.

The aroB gene of Salmonella typhimurium, encoding dehydroquinate synthase, has been cloned into pUC19 and the DNA sequence determined. The aroB gene was isolated from a cosmid gene bank by complementation of an Escherichia coli aroB mutant and screening by Southern blot analysis. The nucleotide sequence of the S. typhimurium aroB gene revealed the presence of an open reading frame, encoding a protein of 362 amino acids with a calculated molecular mass of 38696 Daltons. The amino acid sequence of S. typhimurium dehydroquinate synthase is nearly identical to the E. coli homologue and shows high homology with other aroB gene products from other organisms. Subsequently, a stable insertional mutation in aroB was introduced into the wild-type S. typhimurium C5 strain. This mutant was auxotrophic for aromatic compounds. Infection of BALB/c mice with this mutant demonstrated attenuation comparable to other S. typhimurium mutants unable to biosynthesize aromatic amino acids.