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phase; r i tilnnientous species o f Helicoli‘ictcv i i has also been isolated recently ( 8 ) . ] Most authors have assumed that if bacteria induce cancer they would d o s o by i causing inflammation, or by producing mutagenic carcinogens in situ. For example, Ohshimii & Bartsch (9) suggested that i tumours result from DNA damage ciiiised i when bacteria generate active oxygen species i and nitric oxide. A n alternative hypothesis, which I wish i t o propose, is t h t Gy p r o d w i n g LIV light i i i h n groiifing iitithin o r IietiLleen body cells, / i t i c t ( v i ~c ~~ i i i s eD N A rnirt~itionsi i h i c h in tirrn i cl?11 S e CCI n ce r . This hypothesis firstly requires that bacteria are present in pre-cancerous cells i and tuniours. As mentioned above there is considerrible historical, as well as recent, ! evidence to show that this is the case. Chari ! et al. ( l o ) , using a sensitive PCR-ELISA method, have shown that mycoplasma conserved DNA is prevalent in malignant i ovarian cancer. It is noteworthy that these authors describe mycoplasmas a s ‘tiny poly- i Hypothesis can UV morphic prokaryotic organisms that lack a produced by intracellular cell wall and reside ubiquitously at the cell ! membrane or internalized within the cell’. i bacteria cause cancer? That is they correspond to what historically has been termed the ‘symplasni’ or hidden In eii rl ie r con t r i but i on s to M ic roliiology Comment I discussed (with others) the i phase of the ‘cancer germ’. A second, obvious requirement o f the i possibility that, by producing UV, microorganisms might intluence the growth o f i hypothesis is that bacteria must be iible to adjacent cells ( I ) , and that there is consider- i produce U V light. The ability of living cells, including i able evidence to suggest that bacteria arid bacteria, to produce UV and visible light as other non-viral micro-organisms may cause cancer (2).A n interesting hypothesis develops i part of their normal metabolism is now i when these two possibilities nre joined i well-established ( 1 I ) . Tilbury & Quickenden i together, namely that some cancers result i ( I Z ) , for example, have shown that when bncteria produce mutagenic U V light ! Esclwrichi‘i coli produces weak luminescence i during aerobic growth, the first period of in sitii. Consideriible historical and recent evidence i emission occurring during exponential growth and comprising :i UV band (210- i suggests thiit bacteria nnd other non-viral micro-organisms can readily be isolated from i 330 nm) 3 s well as a visible region (450- i 620 n n i ) . Similar emissions have also been human tumours (3) and that rather than being harmless contaminants, they may c:iiise i reported in Scrcc/~aronrycc~sc m j t k i ‘ i c ( 13). cancer. Such so-called ‘cmicer germs’ often i As yet, however, no one has tested the i possibility thiit (a) bacteria isolated from lack cell walls, exhibit extreme pleomorphisni and app:ireiitIy reside within cancerous cells i cancers can emit U V or visible light and i (4, 5 ) . The link between cancer and bacterial i (b) if they do, whether such emissions lire i infection hns been strengthened by the recent i produced by bacteria when growing in situ in the body It would also be interesting i findings that HelicobrictcJr pylori, the cause o f to know if H . pylori produces U V when stomach ulcers, is also involved in the aetiology of gastric cancer (6,7).[ H . pylori shows ! growing in the stomach lining; such emissions might induce celluliir changes that lead to i limited pleornorphism in having a coccoidal - Microbiology 144, December 1998 ; Downloaded from www.microbiologyresearch.org by IP: 88.99.165.207 On: Thu, 15 Jun 2017 14:11:04 the formntion o f ulcers :is well :is tuiiioiirs. Could this UV, produced by bacteria, induce cnncers? The mutagenic properties o f U V are o f course well-known. Kielbassa et t d . (14) found that DNA damage to Chinese hamster cells was induced by UV and visible light (290400 nm). Such emissions, if produced in sitir, might induce DNA damage and ultimately the formation o f cancers. Illingworth (IS) also suggested that cmicer niay result when body cells themselves produce potentially mutagenic UV. While this may be the case, UV and visible light produced by bacteria, growing within cells and in close proximity to the iiiicleus, might be expected t o be more intense and cai~se more damage to DNA than woiild cellular UV. Bacteria can live within cells for extended periods, ;is so-called ‘persistors’, in which form they can avoid the immune system and the effects of mtibiotics. In terms o f DNA damage, the ability of bacteria to grow intracellularly and emit U V over long periods might help compensate for the ultra-weak nature o f bacterial UV emissions. It is iilso worth noting that polyaromatic hydrocarbons (PAHs, which incidentally are produced in cigarette smoke) can induce cancers, including those of the breast (16), and secondly, that UV light (300-400 mi) is known to enhance the carcinogenic effects b GUlDELlNES Communications should be in the form o f letters and should be brief arid to the point. A single small Table o r Figure niay be included, as may a limited iiuniber of references (cited in the text by numbers, and listed in alphabetical order at the end of the letter). A short title (fewer than SO characters) should be provided. Approval for publication rests with the Editor-in-Chief, who reserves the right to edit letters and/or to niake a brief reply Other interested persons may also be invited to reply. The Editors o f Microbiologyd o not necessarily agree with the views expressed in Microbiology Comment. Contributions should be addressed to the Editor- i n -Ch ief via the Edit o ria 1 0ftice. 3239 Microbiology Comment of these compounds (17). It is therefore possible that cancer may result from synergistic interactions between normal cellular UV light, bacteria-produced UV emissions and pollutants such as PAHs. The suggested hypothesis would help explain why cancer is not infectious in the normal sense, since it implies that the UV produced by bacteria growing within the cell would operate as a ‘cancer switch’ which would also be influenced by both hereditary and environmental factors. The internal production of UV might be one of many ways by which intracellular bacteria might influence the operation of such a ‘switch’. Of course, ‘the devil lies in the detail’ and the main problem with this hypothesis relates to dose-effect. That is would sufficient UV be produced by intracellular bacteria to effect DNA mutagenesis, bearing in mind that any UV emissions would be subject to adsorption by cellular contents, including membranes? Should the present hypothesis be correct, then vaccines might be developed to prevent the growth of intracellular bacteria. Alternatively, other agents might be found which could prevent such bacteria from emitting UV, or counteract its mutagenic effects. Such agents would be invaluable in preventing both the development or spread of cancer. Milton Wainwright Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, 510 2TN, UK. Tel: +44 114 222 4410. Fax: +44 114 272 8697. e-mail: M.WainwrightQshef.ac.uk 1. Wainwright, M.,Killham, K., Russell, C. & Grayston, S. J. (1997). Partial evidence for the existence of mitogenetic radiation. Microbiology 143, 1-3. 2. Wainwright, M.(1997). When heresies collide extreme bacterial pleomorphism and the cancer germ. Microbiology 144,595-596. 3. Wainwright, M.(1995). The return of the cancer germ Soc Gen Microbiol Q 22,48-50. 4. Cantwell, A. R. (1990). The Cancer Microbe. Los Angeles: Aries Press. 5. Hess, D. J. (1997). Can Bacteria Cause Cancer? New York: New York University Press. 6. Eidt, S. & Stolte, M. (1993).Helicobacterpylori and gastric malignancy. Zentbl Bakteriol280, 137-143. 7. Nightingale, T. E. & Gruber, J. (1994). Helicobacter and human cancer. J N a t f Cancer Inst 86,1505-1509. 8. Franklin, C. L., Beckwith, C. S., Livingston, R. S., Riley, L. K., Gibson, S. V., Besch-Williford, C. L. & Hook, R. R. (1996). Isolation of a novel Helicobacter species, Helicobacter cholecystus sp. nov., from the gallbladders of Syrian hamsters with cholangiofibrosis and centrilobular pancreatitis. J Clin Microbiol 34, 2952-2958. 9. Ohshima, H. & Bartsch, H. (1994). Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat Res 305,253-264. 10. Chan, l? J., Seraj, I. M., Kalugdan, T. H. & King, A. (1996). Prevalence of mycoplasma conserved DNA in 3240 malignant ovarian cancer detected using PCR-ELISA. Gynecol Oncol63,258-260. 11. Shen, X.,Liu, F. & Li, X.Y (1993). Experimental study on photocount statistics of the ultraweak photon emission from some living organisms. Experientia 49, 291-295. 12. Tilbury, R.N. & Quickenden, T. I. (1988). Spectral and time dependence studies of the ultraweak bioluminescence emitted by the bacterium Escherichia coli. Photochem Photobiol47,145-150. 13. Quickenden, T.I. & Tilbury, R. N. (1983). Growth dependent luminescence from cultures of normal and respiratory deficient Saccharomyces cerevisiae. Photochem Photobiol37,337-344. 14. Kielbasa, C., Roza, L. & Epe, B. (1997). Wave length dependence of oxidative DNA damage induced by UV and visible light. Carcinogenesis 18, 811-816. 15. Illingworth, J. E. (1986). The relationship between ultraviolet radiation and epithelial cancer. Med Hypotheses 19,155-160. 16. Morris, J. J. & Seifter, E. (1992). The role of aromatic hydrocarbons in the genesis of breast cancer, Med Hypotheses 38,177-184. 17. Arfsten, D.P., Schaeffer, D. J. & Mulveny, D. C. (1996). The effects of near ultraviolet radiation on the toxic effects of polycyclic aromatic hydrocarbons in animals and plants: A review. Ecotoxicol Environ Saf 33,l-24. Reviewer’s Comments At first sight, this hypothesis appears unlikely However, if it is an established fact that micro-organisms do produce UV light, then it is worth considering. One possible way of testing this hypothesis is to look at the profile of mutations induced in a gene such as p53 in tumour cells. Skin cancers show significant levels of mutations at adjacent pyrimidines indicative of UV-damage. If this was shown to be the case for internal tumours this would suggest UV-damage at di-pyrimidine sites, a finding that would strongly support the hypothesis. However, the prevailing data do not show this, certainly not at significant levels. For example, lung tumours, associated with smoking, most often show transversions at G residues, consistent with exposure to PAHs. It may, however, be worth closely examining the mutation data for a variety of internal tumours to determine if UV-associated mutations occur as rare events (particularly in non-smokers). One must also consider the wavelength of UV light produced by these organisms, UV-B and UV-C will produce pyrimidine dimers, whilst UV-A will not. Much less is known about the mutational effects of UV-A which may induce DNA damage indirectly through radical formation and not at dipyrimidines. In summary, this is an interesting hypothesis, which while it might be unlikely, is not outside the bounds of possibility Nigel J. Jones School of Biological Sciences, University of Liverpool Downloaded from www.microbiologyresearch.org by IP: 88.99.165.207 On: Thu, 15 Jun 2017 14:11:04 lntracellular location of mycoplasmas Mycoplasmas associated with animals have generally been regarded as extracellular and their specific attachment to the surface of eukaryotic cells has been widely reported. However, in recent years evidence has accumulated that certain species, including Mycoplasma fermentans, Mycopfasma genitalium and Mycoplasma hominis, may have an intracellular location, and Mycopfasma pertetrarts, isolated from the urine of AIDS patients, has been shown to penetrate a wide range of cultured animal cells (1).The ability of mycoplasmas to survive within host cells is significant and might help explain the chronic nature of many mycoplasma infections and the persistence of asymptomatic carriers. Furthermore, their survival within professional phagocytic cells might lead to dissemination within the host. M . fevmentans has been implicated in human diseases affecting diverse body tissues. We have obtained electron micrographs of M . fermentans (PG18) with human polymorphonuclear leukocytes (PMNL) which show mycoplasmas clustered within phagosomes and also single mycoplasma cells apparently free within the cytoplasm (Fig. 1). There is an apparent interaction between the cytoplasm and these intracytoplasmic mycoplasmas that leads to the formation of an electron-dense layer completely enclosing the mycoplasma cell and approximately 30 nm in thickness. This electron-dense layer may be surrounded by a membrane. The frequency with which intracytoplasmic mycoplasmas were seen was greater where mycoplasma cells were non-opsonized than when non-specifically opsonized by incubation for 45 min in 10 O/O human serum. In contrast, when mycoplasma cells were opsonized, intracellular mycoplasmas were almost always internalized within phagol ysosomes. It has been argued that in electron microscopic studies the appearance of mycoplasmas within cells might be artefactual and due to the presence of the mycoplasmas within invaginations of the cell membrane. Thus, Taylor-Robinson et al. (2) claimed that unequivocal evidence of the intracellular location of mycoplasmas required specific staining of both the mycoplasma and host cell surface. This was achieved in their study using gold-labelled anti-mycoplasma antibody and ruthenium red, which bound to the exposed polysaccharide surface of both mycoplasma and eukaryotic cell surfaces, but not to the membranes of cell vacuoles. Jensen et al. ( 3 ) found ruthenium red staining of the Vero cell membrane to be weak and of little value in confirming the apparent intracellular location. of M . genitalium cells. They argued that where mycoplasma cells appeared close Microbiology 144, December 1998