New classes of environmental tumor promoters: indole alkaloids and polyacetates

Tumor promoters are known to induce ODC activity in mouse skin and that this induction can be inhibited by the application of 13-cis-retinoic acid. These two properties of tumor promoters were utilized for screening new tumor promoters in our environment. Two new classes of tumor promoters are presented: indole alkaloids (teleocidin and lyngbyatoxin A) and polyacetates (aplysiatoxin and debromoaplysiatoxin). Teleocidin from streptomyces and lyngbyatoxin A, from the blue-green alga, Lyngbya majuscula, were able to induce ODC activity in mouse skin and showed various biological activities similar to those of TPA. Teleocidin and lyngbyatoxin A are indole alkaloids. Their tumor promoting activities became apparent in the mouse skin through a two-stage carcinogenicity test. The tumor incidence of the group treated with DMBA plus teleocidin was 100% at week 30, which was similar to that of the group given DMBA and TPA. The in vivo carcinogenicity test with lyngbyatoxin A is still underway. The tumor incidence of the group treated with DMBA plus lyngbyatoxin A is 80% at week 21. A second new class of tumor promoter is polyacetate. Aplysiatoxin and debromoaplysiatoxin were isolated from another variety of blue-green alga. Aplysiatoxin and debromoaplysiatoxin induce ODC to the same degree of potency. However, aplysiatoxin induced various membrane effects, such as adhesion of cells and turnover of phospholipid with a similar concentration of TPA, teleocidin and lyngbyatoxin A. On the other hand, debromoaplysiatoxin required an amount almost 100 times greater to achieve the same effects. We are convinced of the possibility that various classes of tumor promoters exist in our environment.