Attempts at the induction of neoplasia in organ cultures were made in a reasonably systematic way by Heidelberger (1973) after the earlier studies of Lasnitzki (1963). Heidelberger attempted to induce carcinomas in organ culture of rat prostate by the addition of carcinogenic polycyclic hydrocarbons to the cultures. Although significant morphological changes occurred, including squamous metaplasia and cytological anaplasia, no neoplasms were produced when the cultures exhibiting such changes were inoculated into suitable mouse hosts. Later studies by Lasnitzki (1976) in this system demonstrated that retinoids added to the cultures could reverse the mor- phological effects produced by 10 days of incubation with a polycyclic hydrocarbon.
As an extension of these investigations, several investigators have developed an in vitro–in vivo format for carcinogenesis in organ cultures. Basically, the cultures are exposed to carcino- gen for a specific time and then directly reimplanted into syngeneic hosts in order to study the development of neoplasia in vivo in the inoculated host. One example of such a system is the use of mouse mammary epithelial cells exposed to carcinogens and then implanted into the mam- mary fat pads. In such a system, morphological neoplasms of the mammary gland developed (Iyer and Banerjee, 1981; Rivera et al., 1981). In earlier studies, Laws and Flaks (1966) pro- duced a similar effect by treating embryonic mouse lung tissue in organ culture with methyl- cholanthrene for 8 days and subsequent implantation into the flank of syngeneic mice. In more than half of the tissues implanted in vivo, pulmonary adenomas and related lesions developed from the implanted tissue. A difficulty of these experiments was the question of whether or not the original carcinogen had been completely removed from the cultures prior to their inoculation into suitable hosts. Obviously, if this removal had not occurred, one would be dealing merely with carcinogenesis in vivo.