Subcutaneous undifferentiated sarcoma induced by N'-ethyl-N'-nitrosourea in rat: radiology, histopathology and mutagenesis.
The aim of the present study was to investigate high dose and long-term effects of a common industrial agent, N'-ethyl-N'-nitrosourea (ENU), on soft tissues in a rat model. ENU, which was dissolved in polyethyleneglycol (PEG) was injected intra-peritoneally once a week (300 mg/kg) in the first experimental group. The second group received only PEG. The control group was free of any agent administration. Only rats treated with ENU for a period of 45 weeks developed large subcutaneous tumours (approximately 5-9 cm in size). Tumoral tissues were examined radiologically, histopathologically and immunohistochemically. There was no bone destruction beneath the soft tumoral tissues in direct X radiograms. Computed tomographic (CT) images showed heterogeneous soft tissue masses with a density ranging from 50 to 65 HU. Macroscopically, all tumors were circumscribed with a gray-white surface in the cross-sections. The histopathological and immunohistochemical examination of the subcutaneous tumoral tissues showed a spindle cell type of sarcoma. Lymphatic and skeletal muscle invasion, atypical mitoses and necroses were determined in all tumoral tissues in the experimental group. A somatic point mutation was detected in exon 2 of KRAS oncogene in sarcoma tissues using the single strand conformational polymorphism (SSCP) analysis. In conclusion, the activated KRAS oncogene might contribute to the progression of subcutaneous sarcoma in experimentally ENU induced rats due to point mutation.