Download Hypothesis - can UV produced by intracellular

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
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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
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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