[Mechanisms of the tumor promoting effect of 12-0-tetradecanoyl phorbol 13-acetate on the ethylnitrosourea induced transplacental neurogenic carcinogenesis].
To investigate the mechanisms of the tumor promoter, 12-0-tetradecanoyl phorbol 13-acetate (TPA), chromosomal change, [3H]-thymidine incorporation, DNA histogram pattern, and the cellular contents of protein, RNA, and DNA were analyzed with in vivo-in vitro assay to ethylnitrosourea (ENU) induced transplacental neurogenic carcinogenesis. The earlier appearance of chromatid breaks and exchanges was found in the ENU group treated with TPA than that in the ENU group treated with or without acetone. From the findings of cellular DNA contents and DNA histogram pattern, the rapidly increased percentage of G2-M phased population and the rapid increase of cellular DNA contents were found in the ENU group treated with TPA compared to the ENU group. And the more rapid increase of [3H]-thymidine incorporation was found in the ENU group treated with TPA than that in the ENU group. The findings of chromosomal changes, DNA histogram pattern, [3H]-thymidine incorporation, and cellular DNA content in the control group did not differ from that in the control group treated with TPA. Above results seem to be indicated that TPA might modulate the metabolism of nucleic acids and the regulation of gene expression damaged initially by ENU.
D000818:Animals; D001932:Brain Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D002273:Carcinogens; D002869:Chromosome Aberrations / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D005038:Ethylnitrosourea; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D008431:Maternal-Fetal Exchange; D009363:Neoplasm Proteins / Q000032:analysis; D010704:Phorbols / Q000494:pharmacology*; D011247:Pregnancy; D012334:RNA, Neoplasm / Q000032:analysis; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D002273:Carcinogens; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D010704:Phorbols; D012334:RNA, Neoplasm; D013755:Tetradecanoylphorbol Acetate; D005038:Ethylnitrosourea; D013936:Thymidine