Susceptibility to killing by bcg‐activated macrophages associated with ‘spontaneous’ neoplastic transformation in culture

Non‐tumorigenic and ‘spontaneously’ transformed tumorigenic paired cell lines derived from mouse, rat, or hamster embryonic tissues were examined for their susceptibility to killing by mouse peritoneal macrophages activated in vivo by infection with Mycobacterium bovis , strain Bacillus Calmette‐Guérin (BCG). Susceptibility to killing was measured by the extent of clearing in a confluent layer of target cells overlying an area of adherent macrophages or by the release of 3 H counts from target cells prelabelled with [ 3 H]‐thymidine. Only tumorigenic lines showed complete clearing by activated macrophages; the reaction occurred regardless of species differences between macrophages and target cells. The degree of clearing increased with increasing ratio of macrophages to target cells. Normal macrophages from uninfected mice did not produce a clearing reaction. The macrophage reaction discriminated between non‐tumorigenic and tumorigenic cells with short tumor latent periods (<100 days) even when neoplastic and non‐neoplastic cells were derived in culture from the same cell. The more tumorigenic lines ( i.e. , shortest latent period) tended to be more susceptible to killing. Thus, cells spontaneously transformed in culture are more susceptible to killing by activated macrophages than are their non‐neoplastic counterparts. In two cloned lines the enhanced susceptibility to macrophage killing appeared to be a late manifestation of the neoplastic change.