Because household bleach contains 5. A chlorine dioxide generator has been shown effective for decontaminating flexible endoscopes but it is not currently FDA-cleared for use as a high-level disinfectant Chlorine dioxide can be produced by mixing solutions, such as a solution of chlorine with a solution of sodium chlorite In , a chlorine dioxide product was voluntarily removed from the market when its use caused leakage of cellulose-based dialyzer membranes, which allowed bacteria to migrate from the dialysis fluid side of the dialyzer to the blood side However, the biocidal activity of this disinfectant decreased substantially in the presence of organic material e.
No bacteria or viruses were detected on artificially contaminated endoscopes after a 5-minute exposure to superoxidized water and HBV-DNA was not detected from any endoscope experimentally contaminated with HBV-positive mixed sera after a disinfectant exposure time of 7 minutes Hypochlorites are widely used in healthcare facilities in a variety of settings.
A — dilution of 5. For small spills of blood i. Because hypochlorites and other germicides are substantially inactivated in the presence of blood 63, , , , large spills of blood require that the surface be cleaned before an EPA-registered disinfectant or a final concentration solution of household bleach is applied If a sharps injury is possible, the surface initially should be decontaminated 69, , then cleaned and disinfected final concentration Extreme care always should be taken to prevent percutaneous injury.
At least ppm available chlorine for 10 minutes is recommended for decontaminating CPR training manikins Full-strength bleach has been recommended for self-disinfection of needles and syringes used for illicit-drug injection when needle-exchange programs are not available. The difference in the recommended concentrations of bleach reflects the difficulty of cleaning the interior of needles and syringes and the use of needles and syringes for parenteral injection Clinicians should not alter their use of chlorine on environmental surfaces on the basis of testing methodologies that do not simulate actual disinfection practices , Other uses in healthcare include as an irrigating agent in endodontic treatment and as a disinfectant for manikins, laundry, dental appliances, hydrotherapy tanks 23, 41 , regulated medical waste before disposal , and the water distribution system in hemodialysis centers and hemodialysis machines Chlorine long has been used as the disinfectant in water treatment.
Water disinfection with monochloramine by municipal water-treatment plants substantially reduced the risk for healthcare—associated Legionnaires disease , Chlorine dioxide also has been used to control Legionella in a hospital water supply.
Thus, if a user wished to have a solution containing ppm of available chlorine at day 30, he or she should prepare a solution containing 1, ppm of chlorine at time 0. Sodium hypochlorite solution does not decompose after 30 days when stored in a closed brown bottle The use of powders, composed of a mixture of a chlorine-releasing agent with highly absorbent resin, for disinfecting spills of body fluids has been evaluated by laboratory tests and hospital ward trials.
The inclusion of acrylic resin particles in formulations markedly increases the volume of fluid that can be soaked up because the resin can absorb — times its own weight of fluid, depending on the fluid consistency.
One problem with chlorine-releasing granules is that they can generate chlorine fumes when applied to urine Formaldehyde is used as a disinfectant and sterilant in both its liquid and gaseous states. Liquid formaldehyde will be considered briefly in this section, and the gaseous form is reviewed elsewhere The aqueous solution is a bactericide, tuberculocide, fungicide, virucide and sporicide 72, 82, OSHA indicated that formaldehyde should be handled in the workplace as a potential carcinogen and set an employee exposure standard for formaldehyde that limits an 8-hour time-weighted average exposure concentration of 0.
The standard includes a second permissible exposure limit in the form of a short-term exposure limit STEL of 2 ppm that is the maximum exposure allowed during a minute period Ingestion of formaldehyde can be fatal, and long-term exposure to low levels in the air or on the skin can cause asthma-like respiratory problems and skin irritation, such as dermatitis and itching. For these reasons, employees should have limited direct contact with formaldehyde, and these considerations limit its role in sterilization and disinfection processes.
Formaldehyde inactivates microorganisms by alkylating the amino and sulfhydral groups of proteins and ring nitrogen atoms of purine bases Varying concentrations of aqueous formaldehyde solutions destroy a wide range of microorganisms.
Four percent formaldehyde is a tuberculocidal agent, inactivating 10 4 M. The formaldehyde solution required 2 hours of contact to achieve an inactivation factor of 10 4 , whereas glutaraldehyde required only 15 minutes. For these reasons and others—such as its role as a suspected human carcinogen linked to nasal cancer and lung cancer , this germicide is excluded from Table 1.
When it is used, , direct exposure to employees generally is limited; however, excessive exposures to formaldehyde have been documented for employees of renal transplant units , , and students in a gross anatomy laboratory Formaldehyde is used in the health-care setting to prepare viral vaccines e.
To minimize a potential health hazard to dialysis patients, the dialysis equipment must be thoroughly rinsed and tested for residual formaldehyde before use.
Paraformaldehyde, a solid polymer of formaldehyde, can be vaporized by heat for the gaseous decontamination of laminar flow biologic safety cabinets when maintenance work or filter changes require access to the sealed portion of the cabinet.
Glutaraldehyde is a saturated dialdehyde that has gained wide acceptance as a high-level disinfectant and chemical sterilant Aqueous solutions of glutaraldehyde are acidic and generally in this state are not sporicidal. Once activated, these solutions have a shelf-life of minimally 14 days because of the polymerization of the glutaraldehyde molecules at alkaline pH levels.
This polymerization blocks the active sites aldehyde groups of the glutaraldehyde molecules that are responsible for its biocidal activity. Novel glutaraldehyde formulations e. However, antimicrobial activity depends not only on age but also on use conditions, such as dilution and organic stress. However, two studies found no difference in the microbicidal activity of alkaline and acid glutaraldehydes 73, The biocidal activity of glutaraldehyde results from its alkylation of sulfhydryl, hydroxyl, carboxyl, and amino groups of microorganisms, which alters RNA, DNA, and protein synthesis.
The mechanism of action of glutaraldehydes are reviewed extensively elsewhere , The in vitro inactivation of microorganisms by glutaraldehydes has been extensively investigated and reviewed , Spores of C. Microorganisms with substantial resistance to glutaraldehyde have been reported, including some mycobacteria M. Two percent alkaline glutaraldehyde solution inactivated 10 5 M. However, subsequent studies 82 questioned the mycobactericidal prowess of glutaraldehydes.
Suspensions of M. The rate of kill was directly proportional to the temperature, and a standardized suspension of M. An FDA-cleared chemical sterilant containing 2.
Several investigators 55, 57, 73, 76, 80, 81, 84, have demonstrated that glutaraldehyde solutions inactivate 2. Glutaraldehyde is commonly diluted during use, and studies showed a glutaraldehyde concentration decline after a few days of use in an automatic endoscope washer , This emphasizes the need to ensure that semicritical equipment is disinfected with an acceptable concentration of glutaraldehyde.
Data suggest that 1. Chemical test strips or liquid chemical monitors , are available for determining whether an effective concentration of glutaraldehyde is present despite repeated use and dilution. The frequency of testing should be based on how frequently the solutions are used e.
The bottle of test strips should be dated when opened and used for the period of time indicated on the bottle e. The results of test strip monitoring should be documented. The glutaraldehyde test kits have been preliminarily evaluated for accuracy and range but the reliability has been questioned To ensure the presence of minimum effective concentration of the high-level disinfectant, manufacturers of some chemical test strips recommend the use of quality-control procedures to ensure the strips perform properly.
In December , EPA issued an order to stop the sale of all batches of this product because of efficacy data showing the product is not effective against spores and possibly other microorganisms or inanimate objects as claimed on the label Other FDA cleared glutaraldehyde sterilants that contain 2.
Glutaraldehyde is used most commonly as a high-level disinfectant for medical equipment such as endoscopes 69, , , spirometry tubing, dialyzers , transducers, anesthesia and respiratory therapy equipment , hemodialysis proportioning and dialysate delivery systems , , and reuse of laparoscopic disposable plastic trocars Glutaraldehyde is noncorrosive to metal and does not damage lensed instruments, rubber. Glutaraldehyde should not be used for cleaning noncritical surfaces because it is too toxic and expensive.
Colitis believed caused by glutaraldehyde exposure from residual disinfecting solution in endoscope solution channels has been reported and is preventable by careful endoscope rinsing , Healthcare personnel can be exposed to elevated levels of glutaraldehyde vapor when equipment is processed in poorly ventilated rooms, when spills occur, when glutaraldehyde solutions are activated or changed, , or when open immersion baths are used.
Acute or chronic exposure can result in skin irritation or dermatitis, mucous membrane irritation eye, nose, mouth , or pulmonary symptoms , Epistaxis, allergic contact dermatitis, asthma, and rhinitis also have been reported in healthcare workers exposed to glutaraldehyde , Glutaraldehyde exposure should be monitored to ensure a safe work environment. The silica gel tube and the DNPH-impregnated cassette are suitable for monitoring the 0. The passive badge, with a 0. ACGIH does not require a specific monitoring schedule for glutaraldehyde; however, a monitoring schedule is needed to ensure the level is less than the ceiling limit.
For example, monitoring should be done initially to determine glutaraldehyde levels, after procedural or equipment changes, and in response to worker complaints Engineering and work-practice controls that can be used to resolve these problems include ducted exhaust hoods, air systems that provide 7—15 air exchanges per hour, ductless fume hoods with absorbents for the glutaraldehyde vapor, tight-fitting lids on immersion baths, personal protection e. If engineering controls fail to maintain levels below the ceiling limit, institutions can consider the use of respirators e.
In general, engineering controls are preferred over work-practice and administrative controls because they do not require active participation by the health-care worker. Court of Appeals , limiting employee exposure to 0.
If glutaraldehyde disposal through the sanitary sewer system is restricted, sodium bisulfate can be used to neutralize the glutaraldehyde and make it safe for disposal. The literature contains several accounts of the properties, germicidal effectiveness, and potential uses for stabilized hydrogen peroxide in the health-care setting.
Published reports ascribe good germicidal activity to hydrogen peroxide and attest to its bactericidal, virucidal, sporicidal, and fungicidal properties Tables 4 and 5 The FDA website lists cleared liquid chemical sterilants and high-level disinfectants containing hydrogen peroxide and their cleared contact conditions.
Hydrogen peroxide works by producing destructive hydroxyl free radicals that can attack membrane lipids, DNA, and other essential cell components. Catalase, produced by aerobic organisms and facultative anaerobes that possess cytochrome systems, can protect cells from metabolically produced hydrogen peroxide by degrading hydrogen peroxide to water and oxygen.
This defense is overwhelmed by the concentrations used for disinfection , Hydrogen peroxide is active against a wide range of microorganisms, including bacteria, yeasts, fungi, viruses, and spores 78, Bactericidal effectiveness and stability of hydrogen peroxide in urine has been demonstrated against a variety of health-care—associated pathogens; organisms with high cellular catalase activity e. Synergistic sporicidal effects were observed when spores were exposed to a combination of hydrogen peroxide 5.
Other studies demonstrated the antiviral activity of hydrogen peroxide against rhinovirus The product marketed as a sterilant is a premixed, ready-to-use chemical that contains 7.
Protection from genital wart viruses is important to public health because lesions caused by these viruses can progress to cancer, most notably cancer of the uterine cervix. This cancer causes 5, deaths per year in women in the U. In the developing world, cervical cancer is the number one cause of cancer related deaths in women. Worldwide, , women die annually from this form of cancer. Prevention of HPV infection could prevent most of these cancers.
HPV infection may also lead to other cancers in the ano-genital tracts of women and men. HPV is frequently associated with vulvar and anal cancers. Prevention from transmission could also protect men and women from development of these cancers. It is thought that about one in four women are infected by these viruses in the genital tract, with 1 to 3 percent of women showing overt signs of clinical infection upon gynecologic examination.
Although most infected people do not develop cancer, individuals with HPV worry about infecting their partners, suffer from physical repercussions including possible loss of fertility and fear the development of cancer. Many people with HPV infection are unaware that they are infected. HPV infections occur commonly in adolescents and in people during their reproductive years.
These conditions sensitize MCF7 toward apoptosis, reversing their tamoxifen-resistant phenotype. Mito, mitochondria. In this context, we observed that the addition of tamoxifen plus dasastinib was indeed sufficient to prevent stromal-based tamoxifen-resistance and restore sensitivity toward tamoxifen-induced apoptosis in cancer cells.
Interestingly, under these same coculture conditions, treatment with catalase to neurtralize hydrogen peroxide, prevented ROS production and dramatically induced apoptosis in co-cultured MCF7 cancer cells. Since cancer cells and tumors both produce large amounts of hydrogen peroxide, 7 — 10 the detection of hydrogen peroxide production may be an important new approach toward cancer diagnosis and for the development of novel imaging techniques.
For example, cancer patients such as those with breast and lung tumors can be distinguished from normal controls, based on the detection of hydrogen peroxide in their exhaled breath. Finally, new imaging probes have also been invented that can detect hydrogen peroxide production in pre-clinical models, such as human tumor xenografts.
In further support of this notion, PET imaging with FDG can be effectively used to detect many distinct inflammatory diseases, both of infectious and non-infectious origins. These conditions include fever of unknown origin FUO and bacteremic foci, as well as graft rejection in liver and renal transplants. In summary, hydrogen peroxide is a known carcinogen, and is associated with mutatgenic potential, resulting in a positive Ames test in bacteria.
Thus, we propose that carcinogenesis may be a 3-step process, related to hydrogen peroxide production, as outlined in Figure 5A and B. In this cascade or chain of hydrogen peroxide production, ROS and oxidative stress is passed from the oncogenic stimulus and normal epithelial cells step 1 , to the cancer cells step 2 , and then to the tumor stroma step 3. Step 1 is hydrogen peroxide induced tumor initiation, while steps 2 and 3 are hydrogen peroxide induced tumor progression and metastasis.
Three-step carcinogenesis: hydrogen peroxide in tumor initiation, progression and metastasis. A Tumor Initiation step 1. Oncogenic stimuli such as carcinogens, UV rays, inflammation and aging initiate hydrogen peroxide production, leading to DNA damage in normal epithelial cells.
This leads to the formation of cancer cells, via mutagenesis and ensuing genomic instability. B Tumor Progression and Metastasis steps 2 and 3. Once cancer cells are formed via oncogene activation in normal epithelial cells, then these cancer cells also begin to produce and secrete hydrogen peroxide Step 2 to promote tumor-stroma co-evolution and metastasis Step 3.
In part a, cancer cells secrete hydrogen peroxide, which induces oxidative stress in neighboring stromal cells, such as fibroblasts.
In part b, oxidative stress in fibroblasts leads to ROS production in the tumor stroma, which then further mutagenizes the cancer cells, allowing them to evolve to a more aggressive state, driving stromal lactate production and metastasis. Finally, in part c, hydrogen peroxide and rOs production could also mutagenize adjacent normal epithelial cells, further driving the formation of new cancer cells. Komen Breast Cancer Foundation. Ralph and Marian C. Falk Medical Research Trust.
Funds were also contributed by the Margaret Q. Landenberger Research Foundation to M. This project is funded, in part, under a grant with the Pennsylvania Department of Health to M.
The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. National Center for Biotechnology Information , U. Journal List Cell Cycle v. Cell Cycle. Published online Aug 1. Author information Article notes Copyright and License information Disclaimer. Corresponding author. Correspondence to: Michael P.
Lisanti and Federica Sotgia; Email: gro. Received Jun 9; Accepted Jun This article has been cited by other articles in PMC. Abstract In , Dr. Open in a separate window. Figure 1. Hydrogen Peroxide and the Warburg Effect in the Tumor Stroma: Metabolic Coupling If cancer cells produce and secrete hydrogen peroxide, then this also has important metabolic consequences for the tumor microenvironment.
Figure 2. Hydrogen Peroxide and the Lactate Shuttle As discussed above, cancer cells use hydrogen peroxide as a weapon to extract nutrients from adjacent fibroblasts, via the stromal induction of autophagy and mitophagy. Figure 3. Oxidative Stress, Metabolic-Coupling and Drug Resistance What if acquired resistance to chemotherapeutic agents was a metabolic and stromal phenomenon?
Figure 4. Clinical Utility of Hydrogen Peroxide for Cancer Diagnosis Since cancer cells and tumors both produce large amounts of hydrogen peroxide, 7 — 10 the detection of hydrogen peroxide production may be an important new approach toward cancer diagnosis and for the development of novel imaging techniques.
Summary: Hydrogen Peroxide in Tumor Initiation, Progression and Metastasis In summary, hydrogen peroxide is a known carcinogen, and is associated with mutatgenic potential, resulting in a positive Ames test in bacteria. Figure 5. Acknowledgments F. References 1. Mitochondrial stress signals revise an old aging theory.
Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue. Aging Cell. Extension of murine life span by overexpression of catalase targeted to mitochondria. Gil Del Valle L. Oxidative stress in aging: Theoretical outcomes and clinical evidences in humans.
Biomed Pharmacother. Blagosklonny MV. Increasing healthy lifespan by suppressing aging in our lifetime: preliminary proposal. Aging: past, present and future. Aging Albany NY ; 1 :1—5. Production of large amounts of hydrogen peroxide by human tumor cells.
Cancer Res. Burdon RH. Superoxide and hydrogen peroxide in relation to mammalian cell proliferation. Free Radic Biol Med.
Live imaging of innate immune cell sensing of transformed cells in zebrafish larvae: parallels between tumor initiation and wound inflammation.
PLoS Biol. ROS upregulation mediates Ras-induced changes of cell morphology and motility. Exp Cell Res. Timing of supplementation with the antioxidant N-acetyl-L-cysteine reduces tumor multiplicity in novel, cancer-prone p53 haploinsufficient Tg. AC v-Ha-ras transgenic mice but has no impact on malignant progression.
Nutr Cancer. Transformed and tumor-derived human cells exhibit preferential sensitivity to the thiol antioxidants, N-acetyl cysteine and penicillamine. Stem Cells Dev. The impact of redox and thiol status on the bone marrow: Pharmacological intervention strategies. Pharmacol Ther. A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Oxidative stress promotes myofibroblast differentiation and tumour spreading. Hydrogen peroxide is a diffusible paracrine signal for the induction of epithelial cell death by activated myofibroblasts.
Hydrogen peroxide-mediated nuclear factor kappaB activation in both liver and tumor cells during initial stages of hepatic metastasis. Cancer Sci. Dai DF, Rabinovitch P. Mitochondrial oxidative stress mediates induction of autophagy and hypertrophy in angiotensin-II treated mouse hearts. Med Sci Monit. HIF1alpha functions as a tumor promoter in cancer associated fibroblasts, and as a tumor suppressor in breast cancer cells: Autophagy drives compartment-specific oncogenesis.
Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells. Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFkappaB activation in the tumor stromal microenvironment. Cancer Biol Ther. Human skin keloid fibroblasts display bioenergetics of cancer cells.
J Invest Dermatol. Differential apoptosis markers in human keloids and hypertrophic scars fibroblasts. Mol Cell Biochem. Inadequate blood supply persists in keloids. Warburg O. On respiratory impairment in cancer cells. On the origin of cancer cells. The tumor-promoting effect of wounding: a possible role for TGFbetainduced stromal alterations. Crit Rev Oncog. Fidler IJ. Nat Rev Cancer. AACR centennial series: the biology of cancer metastasis: historical perspective.
Metastasis: the seed and soil theory gains identity. Cancer Metastasis Rev. Cytokine production and inflammation drive autophagy in the tumor microenvironment: Role of stromal caveolin-1 as a key regulator.
0コメント