Distinct responses of 3T3-L1 cells to dihydroteleocidin B and the phorbol ester tumor promoters: relation to adipocyte differentiation, DNA synthesis and cell division.
We have recently shown that an indole alkaloid tumor promoter, dihydroteleocidin B (DHTB) is significantly different from the phorbol ester tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate (TPA) in its potency and mode of inhibiting the adipocyte differentiation of 3T3-L1 cells (1). DHTB almost completely inhibited the differentiation induced by dexamethasone (DEX) and 1-methyl-3-isobutylxanthine (MIX) regardless of when the tumor promoter was added: before, during, or after the addition of inducers. Similar inhibition was observed by TPA with over 90% less efficiency and only when it was added during the inducer treatment. Both DHTB and TPA stimulated DNA synthesis to the same level during the initial 22 hr. The DNA synthesis of resting 3T3-L1 cells triggered by DHTB resulted in cell division, whereas TPA-stimulated DNA synthesis did not facilitate cell division. This observation is in sharp contrast to the previous findings that both DHTB and TPA stimulate a number of growth-arrested fibroblasts (2), including Swiss/3T3 from which 3T3-L1 cells were derived, to initiate DNA synthesis and undergo cell division (3). In order to further clarify this point we attempted to isolate cell variants which were no longer responsive to the mitogenic action of DHTB. Among 14 variant lines isolated, we found two stable variant lines, 1-2 and 2-3, whose DNA synthesis was not initiated by DHTB. DNA synthesis of another variant line, 3-4, was stimulated by DHTB but not followed by cell division. From these findings it is proposed that the modes of action of DHTB and TPA are similar in triggering DNA synthesis of G1-arrested 3T3-L1 cells, but DHTB can further act on 3T3-L1 cells at a point during or after S phase to stimulate events of mitosis.
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects*; D000818:Animals; D002273:Carcinogens; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects; D008235:Lyngbya Toxins / Q000633:toxicity*; D051379:Mice; D010703:Phorbol Esters / Q000633:toxicity*; D010704:Phorbols / Q000633:toxicity*
D002273:Carcinogens; D008235:Lyngbya Toxins; D010703:Phorbol Esters; D010704:Phorbols; D004247:DNA; C022229:dihydroteleocidin B