Cellular progression of neoplasia in the subcutis of mice after implantation of 3,4-benzpyrene

Abstract

An implantation model has been used to investigate the cellular progression of chemically induced subcutaneous neoplasia in the mouse. Implantation of 3,4-benzpyrene induced persistent changes in the normal process of connective tissue formation around the implant. Light-microscope and autoradiographic studies have shown a temporal progression from aberrant filter- or muscle-associated cells through proliferative foci to large invasive sarcoma. Electron microscopy revealed that presarcomatous cell foci consisted of one of two different cell types. These were either spindle cells with ultrastructural characteristics similar to foreign-body-induced sarcoma, or cells with the ultrastructural features of rhabdomyosarcoma. The subsequent appearance of two histological groups of sarcoma that were ultrastructurally similar to the cells of the early proliferative foci indicated that both elements may progress to form tumours. However, the constituent cells of both groups of tumours displayed a broad histological and ultrastructural spectrum and the marked similarity between the undifferentiated cells of each suggested that both may have arisen from diverse differentiation of a common pluripotential cell such as the pericyte. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9

Analysis of cell cultures of 3,4-benzpyrene-treated subcutis and subsequent growth in semi-solid medium

“…The appearance of these cells mirrored the inflammatory reaction that had occurred in vivo (Westwood et al, 1979). Fibroblast-like and macrophage-like cells were a dominant feature of these tissue cultures.…”

“…Fibroblastlike cells (Type 4) were typical of the young fibroblasts described by Ham (1974) that occur in tissue sections. These cells were also very similar to the fibroblast-like cells that have been reported to grow from explanted s.c. implants of plastic (Johnson et al, 1977 (Westwood et al, 1979) Agar colonies taken from the 4-week BP-treated explant cultures were found on growth in liquid medium to consist of cells of the described Type 5 morphology. Montagnier & Macpherson (1964) showed that polyoma virus-transformed BiHK cells had the capacity to grow in a semi-solid agar medium whereas normal cells did not.…”

“…Cells of Type 5 morphology were very similar to the large aberrant cells that appeared in vivo after the s.c. implantation of BP, and evidence has been presented for a temporal progression of these cells to form tumours (Westwood et al, 1979). Aberrant skeletal-muscle cells have also been implicated in the s.c. progression of BP-induced neoplasia (Westwood et al, 1979).…”

“…The implantation of carcinogens suspended in gelatin and mounted on Millipore filters has been used in our laboratories as a model to predict the carcinogenicity of materials (Purchase et al, 1976(Purchase et al, , 1978 and to trace the cellular progression of 3,4-benzpyrene-induced neoplasia in the subeutis of mice (Westwood et al, 1979). These latter studies illustrated that pretumour foci of cells were not discernible until 2-3 months after implantation.…”

Spontaneous fibrous histiocytic neoplasms in rats

“…The major part of the study comprised an examination of the tissues of 900 control rats from seven 24-month oral carcinogenicity studiesundertaken at the Centre de Recherche, Pfizer, Amboise, between 1972 and1979. An evaluation of the clinical and pathological data was made in order to study the histological characteristics and behaviour of these neoplasms and, in this respect, a further 3280 rats, taken either from the treated groups of the above studies or controls from shorter studies, were similarly examined to augment an assessment of tumour progression with respect, particularly, to metastasis.…”