[Studies on mechanism of carcinogenesis in cell culture. III. Butyric acid-induced phenotypic reversion of malignant transformed Syrian hamster lung cells (BHLB4)].

The MNNG transformed Syrian hamster lung fibroblast cell line (BHLB4) established in our laboratory was treated with 2.0 mmol/L butyric acid. We obtained a butyric acid-dependent partially reversed cell line (ButB4) similar to normal cells in morphology, membrane properties, proliferation rate, colony-forming ability on solid agar culture, etc. However, when transplanted into nude mice, this cell line's tumorigenicity remained intact. Detection of cAMP levels in the cytoplasm showed much higher levels in ButB4 cells than in transformed cells. Butyric acid activity is evidently associated with changes of cAMP. In addition to phenotypical analysis, the karyotypes of ButB4 and BHLB4 were analyzed in detail. It was found that the disomy rate of C15 was significantly increased in ButB4 cells (73%) as compared with BHLB4 cells (33%). These results show that butyric acid not only induces phenotypic reversion in BHLB4 cells directly, but can also selectively kill C15 monosomy cell clones, allowing rapid growth of C15 disomy cell clones. Butyric acid may also influence maintenance of the reversion phenotype.