DNA Repair Enzyme Decreases Skin Cancer Incidence in Animals

DNA Repair Enzyme Decreases Skin Cancer Incidence in Animals

BUENOS AIRES-Ultraviolet (UV) radiation contributes to skin cancer
induction not only by transforming normal cells to cancer cells
but also by impairing the host immune response to skin cancer,
said Daniel Yarosh, PhD, president of Applied Genetics, Inc.,
Freeport, NY.

Speaking at the 6th World Congress on Cancers of the Skin, Dr.
Yarosh described a series of experiments showing that a liposome-encapsulated
enzyme, T4N5, under development by Applied Genetics, may be able
to inhibit UV-induced DNA damage, thus reducing immune system
suppression and ultimately lowering the risk of skin cancer.

Dr. Yarosh stated that UV radiation produces two major types of
DNA damage: pyrimidine dimer (PD) formation and 6-4 photoproducts.
Mutations activating the ras oncogenes and inactivating p53 tumor
suppressor genes have been sequenced from human skin cancer DNA,
and these mutations occur most frequently at cytosine-pyrimidine
sequences, implicating UV-induced PD formation.

Dr. Yarosh's group, in collaboration with Dr. Margaret Kripke,
University of Texas M.D. Anderson Cancer Center, tested the hypothesis
that UV-induced DNA damage is the triggering event for UV-induced
immune suppression. Their approach involved the use of a DNA repair
enzyme (T4 endonuclease V) that initiates the removal of UV-induced
PDs from DNA, activating DNA repair prior to cell division. The
enzyme is encapsulated in liposomes, called T4N5 liposomes, that
are used to deliver the enzyme into cells of the skin.

Initial Experiments

In the initial experiments, Dr. Yarosh said, purified T4 endonuclease
V, encapsulated in liposomes and delivered to UV-irradiated cells
in culture, increased PD removal and DNA repair synthesis, and
enhanced survival of repair-deficient cells.

Subsequent animal studies involved UV irradiation of the SKH-1
hairless mouse. Unirradiated mice do not produce spontaneous skin
tumors, but mice irradiated three times a week with 1 minimal
erythemal dose of UV-B radiation develop skin squamous cell carcinomas.


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