Enhanced expression of alpha-fetoprotein gene in cultured rat liver epithelial cells treated with N-methyl-N'-nitro-N-nitrosoguanidine.
The expression of alpha-fetoprotein (AFP) gene in a cultured normal rat liver epithelial cell line (WB-F344) and its chemical carcinogen-treated clonal derivatives was examined. WB-F344 cells expressed low levels of AFP and albumin mRNAs. Clonal cell strains and tumor cell lines derived from WB-F344 cells which had been treated multiple times with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) showed heterogeneous levels of expression of AFP mRNA. Enhanced expression was seen in 8 of 18 (44%) cell strains/lines which expressed high gamma-glutamyltranspeptidase (GGT) activity, and in 4 of 6 (67%) of GGT-negative cell strains/lines. Southern blot analyses of DNAs after digestion by HpaII endonuclease indicated that MNNG-treated cells frequently showed hypomethylation of the AFP gene. Tumor cell lines derived from WB-F344 cells which were transformed by a single treatment with MNNG consistently expressed higher levels of AFP mRNA than tumor cell lines derived from spontaneously transformed WB-F344 cells. These results suggest that enhanced expression of AFP in MNNG-treated cultured rat liver epithelial cells may be related to the effect of treatment with this carcinogen, which is known to induce DNA hypomethylation.
Tsao
M S
MS
Department of Pathology, McGill University, Montréal, Qué., Canada.
D000818:Animals; D015139:Blotting, Southern; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D015342:DNA Probes; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D012709:Serum Albumin / Q000096:biosynthesis; D000509:alpha-Fetoproteins / Q000096:biosynthesis*
D015342:DNA Probes; D012333:RNA, Messenger; D012709:Serum Albumin; D000509:alpha-Fetoproteins; D008769:Methylnitronitrosoguanidine; D004247:DNA