422
T .
G .
H S U
graphy at various intervals after labeling, one can tell the entire story
of cell reproduction of this population.
Wide variation in generation time exists among mammalian cell
populations. Most cell lines require something like 20 h or more to
complete one generation. However, a few cases with 11 or 12 h generation time are known. An interesting fact is that regardless of the length
of total generation time, and regardless of the number of chromosomes
per cell, the duration of the S phase is relatively constant (Defendi and
Manson, 1961). The greatest variation occurs in the G x phase (Mendelsohn, 1960a), from a doubtful case of absence in Ehrlich ascites tumor
cells (Hornsey and Howard, 1956) through 1-2 h in a Chinese hamster
cell line (Hsu et al., 1962) and the mouse leukemia L-5178Y (Defendi
and Manson, 1961), 3 h in Ehrlich tumor cells (Edwards, Koch, Youcis,
Freese, Laite and Donalson, 1960) to 12 h or more in L cells (Dewey
and Humphrey, 1962; Whitmore, Stanners, Till and Gulyas, 1961).
Combining cinematography and autoradiography, Sisken and Kinosita
(1961) also showed that changes of generation time by artificial means
are invariably the result of changes in the length of the G x phase.
Application of tritiated thymidine to cell populations has stimulated
many branches of biological research other than directly defining and
determining the length of stages of the cell cycle. Prominent among
these are problems concerning growth, regeneration, and pathology
(Leblond and Walker, 1956; Hughes et al., 1958; Messier, 1959;
Edwards and Klein, 1961). Though not completely settled, it is now
thought that cells synthesizing D N A are preparing for mitosis. Appearance of nonlabeled mitosis in a tissue after the application of H
3 - T D R ,
however, does not constitute evidence against this general concept,
because some cells may begin to synthesize D N A after the labeled
compound has been exhausted in the blood stream or the culture
medium. Nevertheless, the argument to be given below should at least
modify the current thought.
In extensive studies on thymidine uptake among various tissues of
the rat, MacDonald and Mallory (1959) found that some tissues, such
as brain and myocardium, which as a rule do not show mitotic activity,
still incorporate this radioactive D N A precursor. They interpreted this
phenomenon as a suggestion of amitosis. In other words, since it is
assumed that cells which synthesize D N A must soon divide, and since
no mitosis is seen, the division must be in an amitotic fashion. Such
reasoning is unnecessary. All the cases reported in the literature of
presumed amitosis in higher animals lack direct proof and all can be
explained as resulting from previous abnormal mitoses, such as incomplete division or the persistence of chromatin bridges. Incorporation of labeled thymidine does not lend any substantial support to this
T .
G .
H S U
graphy at various intervals after labeling, one can tell the entire story
of cell reproduction of this population.
Wide variation in generation time exists among mammalian cell
populations. Most cell lines require something like 20 h or more to
complete one generation. However, a few cases with 11 or 12 h generation time are known. An interesting fact is that regardless of the length
of total generation time, and regardless of the number of chromosomes
per cell, the duration of the S phase is relatively constant (Defendi and
Manson, 1961). The greatest variation occurs in the G x phase (Mendelsohn, 1960a), from a doubtful case of absence in Ehrlich ascites tumor
cells (Hornsey and Howard, 1956) through 1-2 h in a Chinese hamster
cell line (Hsu et al., 1962) and the mouse leukemia L-5178Y (Defendi
and Manson, 1961), 3 h in Ehrlich tumor cells (Edwards, Koch, Youcis,
Freese, Laite and Donalson, 1960) to 12 h or more in L cells (Dewey
and Humphrey, 1962; Whitmore, Stanners, Till and Gulyas, 1961).
Combining cinematography and autoradiography, Sisken and Kinosita
(1961) also showed that changes of generation time by artificial means
are invariably the result of changes in the length of the G x phase.
Application of tritiated thymidine to cell populations has stimulated
many branches of biological research other than directly defining and
determining the length of stages of the cell cycle. Prominent among
these are problems concerning growth, regeneration, and pathology
(Leblond and Walker, 1956; Hughes et al., 1958; Messier, 1959;
Edwards and Klein, 1961). Though not completely settled, it is now
thought that cells synthesizing D N A are preparing for mitosis. Appearance of nonlabeled mitosis in a tissue after the application of H
3 - T D R ,
however, does not constitute evidence against this general concept,
because some cells may begin to synthesize D N A after the labeled
compound has been exhausted in the blood stream or the culture
medium. Nevertheless, the argument to be given below should at least
modify the current thought.
In extensive studies on thymidine uptake among various tissues of
the rat, MacDonald and Mallory (1959) found that some tissues, such
as brain and myocardium, which as a rule do not show mitotic activity,
still incorporate this radioactive D N A precursor. They interpreted this
phenomenon as a suggestion of amitosis. In other words, since it is
assumed that cells which synthesize D N A must soon divide, and since
no mitosis is seen, the division must be in an amitotic fashion. Such
reasoning is unnecessary. All the cases reported in the literature of
presumed amitosis in higher animals lack direct proof and all can be
explained as resulting from previous abnormal mitoses, such as incomplete division or the persistence of chromatin bridges. Incorporation of labeled thymidine does not lend any substantial support to this
