Evidence suggesting a dissociation of DNA strand scissions and late-stage promotion of tumor cell phenotype.

Abstract

The relationship between the direct (i.e., within the target cell itself) induction by tumor promoters of DNA double or single strand scissions and late-stage promotion of a selected tumor cell phenotype in JB6 mouse epidermal cells was investigated. These cells have been shown to respond to late-stage tumor promoters with an irreversible induction of anchorage independent growth. Mezerein, a late-stage tumor promoter in mouse skin, stimulated promotion of anchorage independent growth of JB6 cells without detectable concomitant induction of DNA double or single strand breaks. A single treatment of JB6 cells with benzoyl peroxide, a complete tumor promoter, or H2O2, a weak complete tumor promoter but an efficient Stage I tumor promoter, did not induce anchorage independent growth but did induce DNA single strand scissions. The lack of induction of detectable DNA strand scissions by mezerein, an active promoter of anchorage independent growth, and the existence of promoters which induce DNA strand scissions but not promotion of anchorage independent growth after a single treatment, suggest that direct induction of DNA strand scissions is unrelated to the late-stage promotion of tumor cell phenotype in JB6 cells.