Promotion of 3'-methyl-4-dimethylaminoazobenzene-initiated adult rat liver cells to malignant state by phenobarbital in culture.
After treatment with 1.5 mM phenobarbital (PB) for about 2 months, non-tumorigenic rat liver epithelial-type cell lines (6F-7 and 6G-5), which were initiated by 3'-methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB) in primary culture, showed an increase in plating efficiency, growth in soft agar and production of tumors in syngeneic animals. However, the PB-untreated control cells exhibited neither growth in soft agar nor production of tumors. Gamma-glutamyltranspeptidase (GGT)-positive (6F-7-cl-7) and negative (6F-7-cl-8) colonial clones, which were derived from 6F-7 cells, were also treated with 1.5 mM PB for about 2 months. The growth of GGT-positive 6F-7-cl-7 cells was not suppressed but rather stimulated by PB at 1.5 mM, whereas that of GGT-negative 6F-7-cl-8 cells was severely inhibited. Furthermore, the PB-treated 6F-7-cl-7 cells produced tumors in syngeneic animals, but the PB-treated 6F-7-cl-8 cells produced no tumors. The spontaneous cell line 6A-6, which was derived from the 3'-Me-DAB-untreated primary liver cell culture and was GGT-negative, did not exhibit tumorigenicity after treatment with 1.5 mM PB for the same period of time as described above. In conclusion, PB treatment efficiently and rapidly promoted the 3'-Me-DAB-initiated cells to a malignant state.
Miyazaki
M
M
Handa
Y
Y
Suzuki
Y
Y
Sato
J
J
D000818:Animals; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004848:Epithelium / Q000187:drug effects; D008099:Liver / Q000166:cytology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D008749:Methyldimethylaminoazobenzene / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000378:metabolism; D004124:p-Dimethylaminoazobenzene / Q000031:analogs & derivatives*
D008749:Methyldimethylaminoazobenzene; D004124:p-Dimethylaminoazobenzene; D005723:gamma-Glutamyltransferase; D010634:Phenobarbital