Soft Tissue Tumors in The Rat

Induction of Sarcomas by a Single Subcutaneous Injection of 7,12-Dimethylbenz[a]anthracene into Neonatal Male Sprague–Dawley Rats: Histopathological and Immunohistochemical Analyses

“…However, we consider that the clusters of atypical mesenchymal cells in Experiment 3 acted as soils or seeds for rhabdomyosarcomas or other sarcomas considering the previous reports of animal experiments that proliferation of atypical fibroblasts or mesenchymal cells (Vasiliev, 1959;Thomas et al, 1977;Nikitin et al, 1993), irregular proliferation of capillaries (Richter et al, 1999), foci of cells with the ultrastructural features of a rhabdomyosarcoma (Westwood et al, 1979) emerge on early days after exposure to chemocarcinogens before overt sarcomas appear.…”

“…We could not confirm at present whether the clusters of atypical mesenchymal cells in Experiment 3 were early neoplastic lesions with the potential to develop into a malignant neoplasm or merely atypical regenerative lesions, because the morphological features of preneoplastic stages of sarcomas are still not well defined (Guillou et al, 1998), and transplantation may be necessary for strict verification of neoplasia. However, we consider that the clusters of atypical mesenchymal cells in Experiment 3 acted as soils or seeds for rhabdomyosarcomas or other sarcomas considering the previous reports of animal experiments that proliferation of atypical fibroblasts or mesenchymal cells (Vasiliev, 1959; Thomas et al, 1977; Nikitin et al, 1993), irregular proliferation of capillaries (Richter et al, 1999), foci of cells with the ultrastructural features of a rhabdomyosarcoma (Westwood et al, 1979) emerge on early days after exposure to chemo-carcinogens before overt sarcomas appear.…”

“…Classification of sarcomas of rats was scarcely done in the past. Thomas tried to classify their induced sarcomas of rats with morphological, electron microscopic and immunohistochemical methods and reported that most of the sarcomas displayed mixed histological pattern, that is, undifferentiated, spindle cell, fibrosarcomatous and rhabdomyosarcomatous areas seen simultaneously (Thomas et al, 1977). In our Experiment 1 and 2, all of the sarcomas did not show immunohistochemically various or colliding pattern in a tumor as for expression of MyoD1, Myoglobin, Desmin, α-SMA and S-100 even though they showed a somewhat mixed morphological pattern.…”

Regulatory Forum Opinion Piece

“…Administration-site MFH is a well-known finding and has been reported in rodent long-term studies with drugs, nongenotoxic chemicals, plant extracts, and inert materials when administered or implanted sc (Bartholomew, Kreeger, and Morton 2014;Thomas et al 1977). Chronic irritation and inflammation were considered to constitute the key etiologic trigger of administration-site MFH (Thomas et al 1977;Stammberger et al 2002;Bartholomew, Kreeger, and Morton 2014). Interestingly, administration-site MFH was seen in preclinical rodent studies with a number of other marketed drugs (Bartholomew, Kreeger, and Morton 2014).…”

“…In a 12-month toxicity study in rats with insulin glulisine and 24-month carcinogenicity studies both in rats and mice with insulin glargine, respectively, treatmentrelated malignant fibrous histiocytoma (MFH) was diagnosed in male and, occasionally, in female rats and mice (Greaves and Faccini 1981;Ward et al 1981) of most groups, including the vehicle control group, at the sc administration site on a background of chronic irritation and inflammation (Stammberger et al 2002; European Medicines Evaluation Agency [EMEA], 2005). Administration-site MFH is a well-known finding and has been reported in rodent long-term studies with drugs, nongenotoxic chemicals, plant extracts, and inert materials when administered or implanted sc (Bartholomew, Kreeger, and Morton 2014;Thomas et al 1977). Chronic irritation and inflammation were considered to constitute the key etiologic trigger of administration-site MFH (Thomas et al 1977;Stammberger et al 2002;Bartholomew, Kreeger, and Morton 2014).…”