52
SIRKKA KUPILA-AHVENNIEMI AND EEVA THERMAN
ture even between 20° and 25°C. Differences in DNA synthesis in the
infected and wounded tissue were not spotted by histochemical methods
by Rasch et al. (1959).
The above-mentioned studies do not, of course, exclude the possibility
of qualitative differences in the DNA of wounded and infected tissues.
The suggestion of Robson et al. (1959) that TIP might be some kind of
extranuclear DNA has not been confirmed (Rasch, 1964). Rasch fed
both the wounded and the infected tissues thymidine3
!! without observing any extranuclear labeling. The attempts to produce tumors with
DNA, extracted either from the crown gall tissue or from the bacteria,
have generally failed (see the literature in Braun, 1962).
Of interest are the studies of Bopp (1960, 1961, 1962, 1964b) who, on
the basis of a number of experiments, has come to the conclusion that the
bacterial stimulus causes a change in the DNA metabolism of the cells
so that the DNA in the tumor cells is qualitatively different from that in
the normal cells. The change can take place only during the first few
days, i.e., during or before the first cell divisions. In his experiments
Bopp has been using analogs of nucleic acid precursors in much the
same way as they have been used in other morphogenetic experiments,
for instance, in the studies on flower induction (e.g., Heslop-Harrison,
1960; Salisbury and Bonner, 1960; Bonner and Zeevaart, 1962; Zeevaart,
1962; Bernier and Bronchart, 1964). The first results of Bopp (1960)
according to which 5-bromouracil inhibits the tumor initiation but not
the wound-healing process or the growth of crown gall bacteria have been
challenged by Lipetz and Stonier (1961) who claimed that certain
samples of 5-bromouracil contained impurities inhibitory to the bacterial
growth. No inhibition of tumor induction was observed by them when
pure samples of 5-bromouracil were added. Bopp (1962), however, maintained that the difference in the results does not depend as much on the
samples of 5-bromouracil as on the virulence of the bacteria used. In the
case of a virulent strain B 6 , 5-bromouracil does not inhibit strongly
enough the formation of the new kind of DNA to prevent tumor formation. Similarly, if enough thymine is available the formation of tumor
DNA is not affected by 5-bromouracil (Bopp, 1961). Whether the inhibitive effect of fluorodeoxyuridine (Bopp, 1964a), recapitulated above,
depends only on its effect on the host mitoses or also on TIP, is not clear
for the present.
Since the attempts to solve the nature of TIP have failed in spite of
the great number of studies and speculative suggestions, many investigators have recently become hesitant to use the term. It must be kept in
SIRKKA KUPILA-AHVENNIEMI AND EEVA THERMAN
ture even between 20° and 25°C. Differences in DNA synthesis in the
infected and wounded tissue were not spotted by histochemical methods
by Rasch et al. (1959).
The above-mentioned studies do not, of course, exclude the possibility
of qualitative differences in the DNA of wounded and infected tissues.
The suggestion of Robson et al. (1959) that TIP might be some kind of
extranuclear DNA has not been confirmed (Rasch, 1964). Rasch fed
both the wounded and the infected tissues thymidine3
!! without observing any extranuclear labeling. The attempts to produce tumors with
DNA, extracted either from the crown gall tissue or from the bacteria,
have generally failed (see the literature in Braun, 1962).
Of interest are the studies of Bopp (1960, 1961, 1962, 1964b) who, on
the basis of a number of experiments, has come to the conclusion that the
bacterial stimulus causes a change in the DNA metabolism of the cells
so that the DNA in the tumor cells is qualitatively different from that in
the normal cells. The change can take place only during the first few
days, i.e., during or before the first cell divisions. In his experiments
Bopp has been using analogs of nucleic acid precursors in much the
same way as they have been used in other morphogenetic experiments,
for instance, in the studies on flower induction (e.g., Heslop-Harrison,
1960; Salisbury and Bonner, 1960; Bonner and Zeevaart, 1962; Zeevaart,
1962; Bernier and Bronchart, 1964). The first results of Bopp (1960)
according to which 5-bromouracil inhibits the tumor initiation but not
the wound-healing process or the growth of crown gall bacteria have been
challenged by Lipetz and Stonier (1961) who claimed that certain
samples of 5-bromouracil contained impurities inhibitory to the bacterial
growth. No inhibition of tumor induction was observed by them when
pure samples of 5-bromouracil were added. Bopp (1962), however, maintained that the difference in the results does not depend as much on the
samples of 5-bromouracil as on the virulence of the bacteria used. In the
case of a virulent strain B 6 , 5-bromouracil does not inhibit strongly
enough the formation of the new kind of DNA to prevent tumor formation. Similarly, if enough thymine is available the formation of tumor
DNA is not affected by 5-bromouracil (Bopp, 1961). Whether the inhibitive effect of fluorodeoxyuridine (Bopp, 1964a), recapitulated above,
depends only on its effect on the host mitoses or also on TIP, is not clear
for the present.
Since the attempts to solve the nature of TIP have failed in spite of
the great number of studies and speculative suggestions, many investigators have recently become hesitant to use the term. It must be kept in