5-Fluorocytosine
Nucleobase analog for in vitro and in vivo cytotoxicity assays
Catalog # sud-5fc
For research use only
Version # 01E24-SV
MECHANISM OF ACTION
PRODUCT INFORMATION
5-Fluorocytosine is deaminated to 5-fluorouracil by cytosine
Content:
deaminase, an enzyme from the pyrimidine salvage pathway. The
5-Fluorocytosine (5-FC) is supplied as one bottle of a colorless, water
cytotoxicity of 5-FU is largely exerted following its conversion, by a
soluble solution at a concentration of 10 mg/ml, filtered to sterility for
two-step route, to 5-fluoro-uridine monophosphate (5-FUMP).
customer convenience.
5-FUMP is further transformed to 5-fluoro-deoxyuridine
- sud-5fc: 250 mg at 10 mg/ml
monophosphate (5-FdUMP), an irreversible inhibitor of thymidylate
Shipping and Storage:
synthase and hence of DNA synthesis by deprivation of deoxy-
5-FC is shipped at room temperature. Store at room temperature in a
thymidine triphosphate (dTTP) (Fig. 1).
cool and dark place.
5-FU can also follow another enzymatic pathway where it is primarily
5-FC is stable for one year when properly stored.
degraded to nontoxic 脽-alanine. To circumvent this catabolic pathway
Quality control:
by orientating 5-FU towards the formation of 5-FUMP, InvivoGen
Activity of the prodrug is controlled by in vitro cytotoxicity assays.
has engineered fusions between E. coli or S. cerevisiae cytosine
deaminase and uracil phosphoribosyltransferase (UPRT) genes. In
SPECIAL HANDLING
prokaryotes and lower enkaryotes, UPRT catalyzes the direct conversion
Caution should be exercised during the handling and disposal of this
of 5-FU to 5-FUMP, whereas in mammalian cells which lack this
product due to potential toxic properties. Wear suitable protective
enzyme, 5-FU is converted to 5-FUMP through the concerted action
clothing when handling this drug. See Materials Safety Data Sheet
of two highly regulated enzymes. Expression of CD::UPRT fusions
(MSDS) for safe handling.
has been demonstrated to increase 5-FC cytotoxicity in cell culture as
well as in vivo.
GENERAL PRODUCT USE
5-Fluorocytosine is a fluorinated analog of cytosine. 5-FC is approved
by the U.S. Food and Drug Administration (FDA) as an antifungal de novo synthesis
agent used for the treatment of Candida and Cryptococcus. Lately
5F-dUMP
with the development of gene therapy, 5-FC has been introduced as a
dUMP dTTP
(5-F)UMP dTMP dTDP
prodrug in combination with the cytosine deaminase suicide gene.
upp
(5-F)uridine
BACKGROUND fur
Mammalian cells are resistant to therapeutic concentrations of codA 尾鈭抋lanine
dihydrouracil
cytosine uracil
5-fluorocytosine due to their lack of cytosine deaminase (CD), an fcy
5-FC 5-FU
enzyme only found in prokaryotes and lower eukaryotes. CD
converts 5-FC into 5-fluorouracil (5-FU), a highly cytotoxic Figure 1: Metabolism of 5-FC. Abbreviations are: codA, E. coli cytosine deaminase;
fcy, S. cerevisiae cytosine deaminase; upp, E. coli uracil phosphoribosyltransferase;
compound routinely used in cancer chemotherapy. 5-FC is used in
fur, S. cerevisiaeuracil phosphoribosyltransferase
combination with the E. coli CD gene (codA) or S. cerevisiae CD gene
(fcy) in suicide gene therapy protocols. To increase the cytotoxicity of
METHOD
5-FC and therefore reduce the concentration of the prodrug
Cytotoxicity assay
administred, InvivoGen has designed E. coli codA::upp and S.
1- Seed cells at a density of 1 x 103 cells/well in a 96-well microtiter
cerevisiae fcy::fur fusion genes (for more details visit our website
plate containing 100 碌l of culture medium.
@ www.invivogen.com).
2- Prepare a set of sterile stock dilutions of the 10 mg/ml solution
CHEMICAL PROPERTIES H2N provided.
CAS n掳: 2022-85-7 3- One day later, add increasing concentrations of 5-FC to the wells.
F
Formula: C4H4FN3O N Note: Remember to include a control well without the prodrug.
Molecular weight: 129.1
4- After 5-7 days, wash cells with fresh medium and assess cytotoxicity
Structure:
by trypan blue exclusion using a hemocytometer to quantify the
O N
results.
H
TECHNICAL SUPPORT
Toll free (US): 888-457-5873
Outside US: (+1) 858-457-5873
E-mail: info@invivogen.com 3950 Sorrento Valley Blvd. Suite A
Website: www.invivogen.com San Diego, CA 92121 - USA
Section 1: Chemical Identification
5-FLUOROCYTOSINE (5-FC)
Commercial product name
CAS Number: 2022-85-7
Catalog Number: sud-5fc
Supplier: InvivoGen 鈥? 3950 Sorrento Valley Blvd, Suite A
San Diego, CA 92121
Tel: 858-457-5873 鈥? Fax: 858-457-5843
Section 2: Physical/Chemical Characteristics
鈥? Boiling Point: No data available
鈥? Vapor Pressure (mm Hg and Temperature): No data available
鈥? Vapor Density (Air = 1): No data available
鈥? Solubility in Water: Soluble
鈥? Specific Gravity (Water = 1): No data available
鈥? Melting Point: No data available
鈥? Evaporation Rate (Butyl Acetate = 1): No data available
鈥? Water Reactive: No data available
鈥? Appearance: Colorless solution
鈥? Odor: None
Section 3: Fire and Explosion Hazard Data
EXTINGUISHER MEDIA: Carbon Dioxide, Dry Chemical Powder or Appropriate Foam.
SPECIAL FIRE FIGHTING PROCEDURES: Firefighters should wear a self-contained breathing
apparatus and protective clothing to prevent contact with eyes and skin.
UNUSUAL FIRE AND EXPLOSION HAZARDS: Upon thermal decomposition, may emit toxic gases.
Section 4: Reactivity Hazard Data
鈥? Reactivity: Stable
鈥? Conditions to Avoid: None listed
鈥? Incompatible Materials: None listed
鈥? Hazardous Composition Products: Upon thermal decomposition, may emit toxic gases including Carbon
Monoxide, Carbon Dioxide and Nitrogen Oxides.
鈥? Hazardous Polymerization: None
Section 5: Health Hazard Data
ACUTE EFFECTS
鈥? Harmful if ingested, inhaled or absorbed through the skin.
CHRONIC EFFECTS
鈥? Possible mutagen
鈥? There have been no adequate trials in animals on the effects of 5-Fluorocytosine on carcinogenesis and
fertility.
PRIMARY ROUTES OF ENTRY
鈥? Ingestion, inhalation, skin absorption
SIGNS AND SYMPTOMS OF EXPOSURE
鈥? May include moderate to severe myocardial toxicity, photosensitivity, nausea, diarrhea, anorexia,
anemia.
EMERGENCY FIRST AID PROCEDURES
鈥? If swallowed, wash out mouth with water provided person is conscious. Call a physician or poison
center immediately.
鈥? In case of skin contact, flush with copious amounts of water for at least 15 minutes. Remove
contaminated clothing and shoes. Call a physician.
鈥? If inhaled, remove to fresh air. If breathing becomes difficult or signs of toxicity exist, consult a
physician. If breathing stops, give artificial respiration and consult a physician.
鈥? In case of contact with eyes, flush with copious amounts of water for at least 15 minutes. Assure
adequate flushing by separating the eyelids with fingers. Seek medical attention.
Section 6: Precautions For Safe handling And Use
STEPS TO BE TAKEN IF MATERIAL IS SPILLED OR RELEASED
Wear chemical-resistant gloves. Take up with sand and or other non-combustible absorbent material and
place into a container and hold for disposal. Ventilate area and wash spill site after pickup is complete.
WASTE DISPOSAL
Burn in a chemical incinerator equipped with an afterburner and scrubber. Observe all federal, state and
local environmental regulation.
PRECAUTIONS FOR SAFE HANDLING AND STORAGE
Store in a tightly closed container at + 15掳 to 25掳C and protect from light. Wear chemical-resistant gloves
and safety goggles while handling. Material should only be handeled by qualified, experienced
professionals.
For Laboratory Use Only. Not for Household Use
The above infromation is believed to be correct but does not purport to be all inclusive and shall be used only as a guide.
InvivoGen shall not be held liable for any damage resulting from handling or from contact with the above product.
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