Fecapentaene-12 (fec-12), a possible initiating agent in colon cancer, is cytotoxic and mutagenic in human fibroblasts. DNA repair deficient fibroblasts are more sensitive than normal fibroblasts to both these effects, which are dose dependent. Further studies with human fibroblasts have shown that fec-12 is a potent inducer of single-strand breaks (SSB) in DNA. A cumulation of these breaks as a result of inhibition of the polymerase component of the excision repair mechanism suggests that their formation may be mediated in part by DNA repair mechanisms. Auto-radiographic techniques have shown that fec-12 is capable of inducing unscheduled DNA synthesis (UDS) in human cells. Further support for the hypothesis that fec-12 is an initiating agent in colon cancer comes from the finding that this compound is an inducer of transformation in murine Balb 3T3 cells. Plasmid assays investigating the nature of fec-12-DNA interaction have shown evidence of interstrand DNA cross-links. Results from electron microscopic studies support these findings and also suggest that fec-12 can directly cause DNA strand breaks.
