Tumor promoter inhibition of intercellular communication between cultured mammalian cells

Cocultures were established of a cell line deficient in hypoxanthine-guanine phosphoribosyltransferase (PG-19; HPRT-) and a mouse epidermal cell line (HEL-37; HPRT+). The cocultures were incubated in a medium containing hypoxanthine, aminopterin and thymidine (HAT). HPRT- cells die in HAT medium unless rescued by metabolic cooperation with HPRT+ cells. The extent of cell death was measured by the release of radioactivity from PG-19 cells previously labelled with [3H]thymidine, and expressed as the lytic index. The lytic index was significantly increased (decreased metabolic cooperation) by tumor-promoting phorbol esters but not by non-promoting esters. The enhanced lytic index was obtained when promoters were incubated with cocultures for 10 h in a total incubation time of 48 h.