Establishment of photoaffinity label derivatives of fluorene as probes in studies of chemical carcinogenesis in mammalian cell culture.
Several azido fluorenes, photosensitive analogs of the established carcinogen 2-acetylaminofluorene, have been synthesized to serve as probes in chemical carcinogenesis and mutagenesis studies. Unlike 2-acetylaminofluorene, these compounds do not require metabolic activation. However, alkylation to critical targets is achieved through the generation of nitrenes by photolysis at 360 nm in situ. We have found that the bifunctional azidofluorenes 2,5-diazidofluorene and 2,7-diazidofluorene were more toxic to and more transforming of the mouse embryo C3H 10T1/2 clone 8 cells when photolyzed in situ than were the monofunctional azides 2-azidofluorene and 7-bromo-2-azidofluorene. When the drugs were photolyzed in phosphate-buffered saline (pH 7.4) and then added to the cells these preirradiated derivatives were not transforming but were slightly toxic. However, there is not relationship between the number of photosensitive azido groups and the cytotoxicities of the preirradiated derivatives as measured by the plating efficiency method. The transformation experiments were performed under conditions in which photolysis was carried out for as little as 15 sec. This is significant because the major events that lead to oncogenesis apparently can occur within this narrow time channel, thereby making the drugs excellent probes in studies in chemical carcinogenesis. Although near ultraviolet light alone may transform the cells (8 to 16 min of irradiation), under the conditions studied ultraviolet light was neither toxic nor transforming.
D000345:Affinity Labels / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005347:Fibroblasts; D005449:Fluorenes / Q000633:toxicity*; D051379:Mice; D010777:Photochemistry; D014466:Ultraviolet Rays
D000345:Affinity Labels; D002273:Carcinogens; D005449:Fluorenes