Effect of microsomally activated AFB1 on GGT activity in 3 rat liver cell lines.

Three cell lines derived from adult rat liver have been used to study changes in levels of gamma-glutamyl transferase (GGT), a possible marker for premalignant transformation in liver in vivo. None of the cell lines was able to metabolize aflatoxin B1 (AFB1) and treatment with AFB1 alone did not influence GGT activity. However, treatment with microsomally activated AFB1 increased the level of activity in a cell line (BL8L) derived from normal liver with very low levels of GGT, by as much as 10-fold, and 5-fold in a cell line (ARL) also isolated from normal rat liver, but which had subsequently undergone spontaneous transformation. Microsomes from rats pretreated with phenobarbitone were compared with those from 3-methylcholanthrene-treated animals. AFB1 activated by the former produced larger increases in GGT activity, but in no case did the enzyme levels approach that in a cell line (JBI) derived from a hepatoma in the liver of an AFB1-fed rat. Treatment of JBI cells with microsomally activated AFB1 produced no further increase in activity. Histochemical staining indicated an uneven distribution of enzyme in all cell populations, both before and after treatment. This cell-culture system is useful for further studies on the role of GGT in carcinogenesis.