GROWTH INDUCED BY DAMAGE
39
microsomal fraction (Tsanev, 1966; Tsanev and Markov, 1964). Recently, Becker and Lane (1965) have presented evidence that almost
immediately after partial hepatectomy there is a breakdown of the endoplasmic reticulum. Therefore the possibility exists that compensatory
hypertrophy is initiated by intracellular damage to critical cytoplasmic
organelles, especially the rough endoplasmic reticulum. Why the sudden
excess of metabolites should result in intracellular damage is not known.
One speculation we can offer is that the influx of the excess of metabolites
into the remaining liver somehow results in an "overwork" of enzymes
that attempt to handle them, resulting in their breakup. This speculation
is supported by the recent work of Slater (1966) who presents evidence
that in order that carbon tetrachloride damage the liver, it must be
metabolized. Thus it may be that both damage-induced growth and
growth induced in compensatory hypertrophy may have much in common,
although the primary stimulus may still be different.
Another form of induced growth of adult tissues is that produced by
transplanted tumors (Argyris, 1966a). For example, T. S. Argyris and
B. F. Argyris (1962b) have shown that subcutaneous transplants of
Erlich ascites tumor invade the overlying skin and stimulate mitotic activity in the epidermis. On the other hand, the resting hair follicles that
are closer to the invading tumor are not stimulated at all. This is particularly interesting because the cells of the outer root sheath of the
hair follicles and those of the epidermis are thought to be developmentally equivalent (Chase, 1954; Montagna, 1962). Tumor transplants
adjacent to the mammary glands of normal or pregnant female mice
result in the stimulation of mitotic activity of the ducts of these glands
(B. F. Argyris and T. S. Argyris, 1959, 1960, 1961a,b; Simmons et al,
1964). But tumor transplants into the liver, kidney, or ducts of lactating
mammary gland of mice do not stimulate mitotic activity of the surrounding cells (Argyris and Trimble, 1964b; Kollar, 1963; Simmons et al,
1964). Spinal and sympathetic ganglia of chick and mouse are stimulated
to grow by the "nerve growth factor," originally isolated from sarcomas
(Levi-Montalcini, 1958).
Tumor-induced growth of adult mammalian organs differs in a number
of ways from growth produced by damage. Tumor-induced growth seems
to be less specific than that induced by damage. The epidermis and the
ducts of the mammary glands of mice respond to the growth-promoting
effects of a variety of epithelial or connective tissue tumors (Argyris,
1966a; T. S. Argyris and B. F. Argyris, 1962a,b), and the nerve ganglia
respond to a wide variety of connective tissue tumors, although not to
39
microsomal fraction (Tsanev, 1966; Tsanev and Markov, 1964). Recently, Becker and Lane (1965) have presented evidence that almost
immediately after partial hepatectomy there is a breakdown of the endoplasmic reticulum. Therefore the possibility exists that compensatory
hypertrophy is initiated by intracellular damage to critical cytoplasmic
organelles, especially the rough endoplasmic reticulum. Why the sudden
excess of metabolites should result in intracellular damage is not known.
One speculation we can offer is that the influx of the excess of metabolites
into the remaining liver somehow results in an "overwork" of enzymes
that attempt to handle them, resulting in their breakup. This speculation
is supported by the recent work of Slater (1966) who presents evidence
that in order that carbon tetrachloride damage the liver, it must be
metabolized. Thus it may be that both damage-induced growth and
growth induced in compensatory hypertrophy may have much in common,
although the primary stimulus may still be different.
Another form of induced growth of adult tissues is that produced by
transplanted tumors (Argyris, 1966a). For example, T. S. Argyris and
B. F. Argyris (1962b) have shown that subcutaneous transplants of
Erlich ascites tumor invade the overlying skin and stimulate mitotic activity in the epidermis. On the other hand, the resting hair follicles that
are closer to the invading tumor are not stimulated at all. This is particularly interesting because the cells of the outer root sheath of the
hair follicles and those of the epidermis are thought to be developmentally equivalent (Chase, 1954; Montagna, 1962). Tumor transplants
adjacent to the mammary glands of normal or pregnant female mice
result in the stimulation of mitotic activity of the ducts of these glands
(B. F. Argyris and T. S. Argyris, 1959, 1960, 1961a,b; Simmons et al,
1964). But tumor transplants into the liver, kidney, or ducts of lactating
mammary gland of mice do not stimulate mitotic activity of the surrounding cells (Argyris and Trimble, 1964b; Kollar, 1963; Simmons et al,
1964). Spinal and sympathetic ganglia of chick and mouse are stimulated
to grow by the "nerve growth factor," originally isolated from sarcomas
(Levi-Montalcini, 1958).
Tumor-induced growth of adult mammalian organs differs in a number
of ways from growth produced by damage. Tumor-induced growth seems
to be less specific than that induced by damage. The epidermis and the
ducts of the mammary glands of mice respond to the growth-promoting
effects of a variety of epithelial or connective tissue tumors (Argyris,
1966a; T. S. Argyris and B. F. Argyris, 1962a,b), and the nerve ganglia
respond to a wide variety of connective tissue tumors, although not to