Res. ViroL 1992, 143, 429-430
(~) INSTITUT PASTEUR/ELsEVIER Paris 1992
L E T T E R TO T H E E D I T O R
Mycoplasmas, transposons and neoplasia F. de St. J. van der Riet tl) and M . J . Renan (2)
a) Department o f Medical Microbiology, University o f Cape Town, Medical School, 7925 Observatory (South Africa), and 12) National Accelerator Centre, PO Box 72, 7131 Faure (South Africa)
Jansson et al. (1991) have renewed interest in the possible causal involvement of mycoplasmas in blood dyscrasia, including leukaemia. However, the possible mechanisms involved remain an enigma. The purpose of this communication is to propose a mechanism involving endogenous transpositional events whereby mycoplasmas could conceivably cause or participate in the causation of neoplasia in man or animals. In an editorial published recently (Editorial, 1992) it was pointed out inter alia that: transposons can change their positions within the genome of the organism that carries them and seem to be ubiquitous in both plant and animal kingdoms; -
-
- - for a long time now, DNA elements with structural features of transposons have been recognized in man; - - the first report of a "jumping gene" that produces an identifiable effect in a human gene was published at the end of last year;
in plants, transposon activity is greatly increased when cells are under replicative stress, especially when chromosomal breakage is occurring. -
-
With regard to the last point, it was suggested that if a similar process takes place in tumour cells, it may contribute to the high mutation rates needed to explain progression to malignancy. In view of the above, we propose that transposon activity may also be increased in animal or human cells when they are under replicative stress, especially when chromosome breakage is occurring. In turn, this could bring about genetic changes in individuals that would result in their developing neoplastic conditions. In this context it is relevant that chromosomal breaks are often associated with neoplasia. Moreover, inasmuch as transposons can act as " g e n e t i c switches" (Travis, 1992), we suggest that transposons may not merely contribute to the high mutation rates needed to explain the
Submitted October 5, 1992, accepted November 3, 1992.
progression to malignancy, but may actually initiate neoplastic processes, some of which could eventually result in malignancy, e.g., by activating the expression of one or more protooncogenes, inactivating tumour suppressor genes or activating oncogenic viruses. Do mycoplasmas play a role in these transposition events? We suggest that they do, based on the following evidence : (1) Mycoplasmas are among the many factors which include chemicals, ionizing radiation and many viruses, some of which are known to be tumorigenic, that affect animal or human ceils in ways (McGarrity et al., 1984) that undoubtedly subject them to replicative stress ; (2) At least in vitro, mycoplasmas can cause a variety of chromosomal aberrations, including chromosomal breaks, in infected cells (McGarrity et ai., 1984). These observations suggest to us that mycoplasma infection may increase the risk of neoplastic
430
F. D E ST. J. V A N D E R R I E T A N D M.J. R E N A N
transformation of the infected cell, by promoting endogenous transposition within that cell. In conclusion, we draw attention to the fact that hamster cells can be transformed by mycoplasmas (MacPherson and Russell, 1966). It should be interesting to investigate whether transposition events are involved here. If they are, this would provide support for the notion that mycoplasmas may cause or participate in causation of
neoplasia by processes involving endogenous transposition events. Key-words: Mycoplasma, Transposon, Neoplasia, Carcinogenesis; Letter to the Editor.
References
Editorial (1992), Transposons: Friends or Foes. Lancet, 339, 215-216. Jansson, E., Wegelius, R., Hakkarai-
nen, K. & Miettinen, A. (1991), Mycoplasmas and leukaemia. (Letter) Res. Virol., 142, 333. McGarrity, G.J., Vanaman, V. & Sarama, J. (1984), Cytogenetic effects of mycoplasmal infection of cell cultures: a review. In vitro, 20, 1-18. MacPherson, I. & Russell, W. (1966), Transformation in hamster cells mediated by mycoplasmas. Nature (Lond.), 210, 1343-1345. Travis, J. (1992), Possible evolutionary rule explored for "jumping genes". Science, 257, 884-885.
(~) INSTITUT PASTEUR/ELsEVIER Paris 1992
L E T T E R TO T H E E D I T O R
Mycoplasmas, transposons and neoplasia F. de St. J. van der Riet tl) and M . J . Renan (2)
a) Department o f Medical Microbiology, University o f Cape Town, Medical School, 7925 Observatory (South Africa), and 12) National Accelerator Centre, PO Box 72, 7131 Faure (South Africa)
Jansson et al. (1991) have renewed interest in the possible causal involvement of mycoplasmas in blood dyscrasia, including leukaemia. However, the possible mechanisms involved remain an enigma. The purpose of this communication is to propose a mechanism involving endogenous transpositional events whereby mycoplasmas could conceivably cause or participate in the causation of neoplasia in man or animals. In an editorial published recently (Editorial, 1992) it was pointed out inter alia that: transposons can change their positions within the genome of the organism that carries them and seem to be ubiquitous in both plant and animal kingdoms; -
-
- - for a long time now, DNA elements with structural features of transposons have been recognized in man; - - the first report of a "jumping gene" that produces an identifiable effect in a human gene was published at the end of last year;
in plants, transposon activity is greatly increased when cells are under replicative stress, especially when chromosomal breakage is occurring. -
-
With regard to the last point, it was suggested that if a similar process takes place in tumour cells, it may contribute to the high mutation rates needed to explain progression to malignancy. In view of the above, we propose that transposon activity may also be increased in animal or human cells when they are under replicative stress, especially when chromosome breakage is occurring. In turn, this could bring about genetic changes in individuals that would result in their developing neoplastic conditions. In this context it is relevant that chromosomal breaks are often associated with neoplasia. Moreover, inasmuch as transposons can act as " g e n e t i c switches" (Travis, 1992), we suggest that transposons may not merely contribute to the high mutation rates needed to explain the
Submitted October 5, 1992, accepted November 3, 1992.
progression to malignancy, but may actually initiate neoplastic processes, some of which could eventually result in malignancy, e.g., by activating the expression of one or more protooncogenes, inactivating tumour suppressor genes or activating oncogenic viruses. Do mycoplasmas play a role in these transposition events? We suggest that they do, based on the following evidence : (1) Mycoplasmas are among the many factors which include chemicals, ionizing radiation and many viruses, some of which are known to be tumorigenic, that affect animal or human ceils in ways (McGarrity et al., 1984) that undoubtedly subject them to replicative stress ; (2) At least in vitro, mycoplasmas can cause a variety of chromosomal aberrations, including chromosomal breaks, in infected cells (McGarrity et ai., 1984). These observations suggest to us that mycoplasma infection may increase the risk of neoplastic
430
F. D E ST. J. V A N D E R R I E T A N D M.J. R E N A N
transformation of the infected cell, by promoting endogenous transposition within that cell. In conclusion, we draw attention to the fact that hamster cells can be transformed by mycoplasmas (MacPherson and Russell, 1966). It should be interesting to investigate whether transposition events are involved here. If they are, this would provide support for the notion that mycoplasmas may cause or participate in causation of
neoplasia by processes involving endogenous transposition events. Key-words: Mycoplasma, Transposon, Neoplasia, Carcinogenesis; Letter to the Editor.
References
Editorial (1992), Transposons: Friends or Foes. Lancet, 339, 215-216. Jansson, E., Wegelius, R., Hakkarai-
nen, K. & Miettinen, A. (1991), Mycoplasmas and leukaemia. (Letter) Res. Virol., 142, 333. McGarrity, G.J., Vanaman, V. & Sarama, J. (1984), Cytogenetic effects of mycoplasmal infection of cell cultures: a review. In vitro, 20, 1-18. MacPherson, I. & Russell, W. (1966), Transformation in hamster cells mediated by mycoplasmas. Nature (Lond.), 210, 1343-1345. Travis, J. (1992), Possible evolutionary rule explored for "jumping genes". Science, 257, 884-885.
