Histological comparison of the growth of rat bladder carcinoma R-4909 observed for two years in vitro and in vivo

Abstract

A transplantable bladder tumor (Chapman R-4909) of the rat, when first received in our laboratory, grew with a complex histopathology. The predominant component was transitional cell carcinoma, but there were foci of keratinization, including pearl formation, and foci of a less well-defined cystic appearance. We report here observations made during the first 2 years of an ongoing study on the divergent histopathology of R-4909 under several conditions of propagation. During the entire period, the tumor has been maintained by serial passage in rats (Fischer 344) and by serial passage in vitro. At intervals, cells of the tissue culture series were inoculated into rats to compare the histopathology of animal- and culture-passed strains. We obtained several clones from the stock cultures and these also were maintained continuously in vitro. At intervals, cells from two of these lineages, clone A and clone B, were inoculated into rats. After 2 years, cells maintained in stock culture, on injection into new rats, produced growths similar to the original in that all three epithelial patterns, transitional, squamous, and adenomatous, were perpetuated. In contrast, the tumor passed exclusively in vivo lost its squamous component completely. It became anaplastic, with tissue architecture almost entirely adenomatous and cystic. Unlike the stock tissue culture line, the clonal isolates following prolonged culture produced adenomatous tumors only. In a related preliminary study, we inoculated into rats R-4909 cells that had been cultivated for up to 2 months under aerobic and anaerobic conditions. Tumors grew in most of the animals, and those of the aerobic group were more cystic than the others.