During eight successive isologous passages of
hepatoma induced in male C3HA mice by
N-nitrosodiethylamine, no common features of
tumor progression were observed, although both the mitotic pattern and ploidy differed from generation to generation. These additional cytologic criteria allowed the biochemical examination of material least changed due to
tumor progression.
Tumor nDNA's were characterized by greater
actinomycin D (AD)- and
acridine orange (AO)-binding abilities than were normal nDNA's; this could have resulted from a higher proportion of double-stranded regions in
tumor DNA. Isolated
tumor deoxyribonucleoprotein had both lower template activity in an
RNA polymerase system and fewer AD- and AO-binding sites, when compared with the activity and sites from normal mouse liver.
RNA-
DNA hybridization data with the above-mentioned findings showed that in
hepatoma, part of the nuclear genome was repressed. Also,
RNA "new classes" appeared and a certain proportion of nuclear genes controlling
mitochondrial protein biosynthesis were derepressed in
tumor mitochondria. The hybridization of
mitochondrial RNA (
mtRNA) and
DNA revealed new classes of pulse-labeled
RNA's in in vitro-incubated liver mitochondria that were absent from intact cell organelles; the hybridization properties of in vivo- and in vitro-formed
hepatoma mtRNA's were similar. Competition and hybridization experiments demonstrated that in
tumor mitochondria in vivo, some new classes of
RNA existed.
Hepatoma mitochondrial
mRNA had a higher metabolic stability than did normal
mRNA.