Ethylnitrosourea経胎盤誘発脳腫瘍における発癌プロモーターの作用—第II報：発癌プロモーターとしてのTPA作用機序

MECHANISMS OF THE TUMOR PROMOTING EFFECT OF 12-0-TETRADECANOYL PHORBOL 13-ACETATE ON THE ETHYLNITROSOUREA INDUCED TRANSPLACENTRAL NEUROGENIC CARCINOGENESIS

　抄録　Ethylnitrosourea （ENU）経胎盤誘発脳腫瘍モデルにおいて，12-0—tetradecanoyl phorbol 13—ace—tate （TPA）の発癌プロモーターとしての作用機序を解明する目的で，ラット胎児脳細胞のin vitroにおける染色体変化，蛋白・RNA・DNA含有量の変化，〔³H〕—thymidine取り込みの変化，およびDNA histo—gram patternの変化に対して検討を加えた。培養10日目には，TPA添加—ENU処理群では，DNA histo—gram pattern上，G_2—M期の細胞が増大し，又この時期に急速な蛋白・RNA・DNA含量の増加と，〔³H〕—thymidine取り込みが認められた。又，染色体分析では，培養30日目頃より，％chromosomal aberrationが増大する所見を認めた。一方，ENU処理群では，DNA histogram pattern上でのG_2—M期の比率の増大，および％chromosomal aberrationの増大はかなり遅れて出現した。又，〔³H〕—thymidineの取り込み，および蛋白・RNA・DNA含量の培養初期一過性増加所見は認められなかった。以上の結果から，TPAの発癌プロモーターとしての作用機序として，ENUに障害された核酸代謝，および遺伝子発現に対する修飾作用が示唆された。

To investigate the mechanisms of the tumor promoter, 12-0-tetradecanoyl phorbol 13-acetate (TPA), chromosomal change, 〔³H〕-thymidine in-corporation, DNA histogram pattern, and the cel-lular contents of protein, RNA, and DNA were analyzed with in vivo-in vitro assay to ethylni-trosourea (ENU) induced transplacentral neuroge-nic 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 G_2-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〕-thy-midine incorporation was found in the ENU group treated with TPA than that in the ENU group. The findings of chromosomal changes, DNA his-togram 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 nu-cleic acids and the regulation of gene expression damaged initially by ENU.