The transformation of a normal cell into a cancer cell is not a sudden
but a slow continuous process which may take years. A systematic study
of the morphological and structural changes that take place during this
cellular transformation has only become possible since methods were
developed to induce a high incidence of tumors in experimental animals.
The growth of such tumors can be followed during all stages of their
development. For several reasons, rat liver has proved to be
particularly suitable. For more than thirty years it has been known that
one can induce tumors in rat liver experimentally with many different
substances. The azo dyes which were used originally (YOSHIDA, 1932;
KINOSITA, 1937) have since been replaced by more potent carcinogens. The
recently discovered nitrosamines, dimethylnitrosamine (MAGEE and BARNES,
1956), diethylnitrosamine (SCHMAHL et aI., 1960) and N-nitrosomorpholine
(DRUCKREY et aI., 1961) should be mentioned in this context. Used in the
proper dose, these carcinogens lead within a few months to the formation
of multicentric hepatomas in practically 100 Ufo of the experimental
animals, and are therefore a very useful tool for studies of the
cytogenesis of cancer (see BUCHNER, 1961; GRUND- MANN, 1961; GRUNDMANN
and SIEBURG, 1962; OEHLERT and HARTJE, 1963; BAN- NASCH and MULLER,
1964). The liver parenchyma as such offers a very big technical
advantage because it consists of a rather homogenous cell population.