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the photosensitization processes occurring
in biological surfaces in contact with sun-
light (Chiarelli-Neto
et al
., 2011).
Singlet oxygen has been shown to
mediate the induction of expression of
several redox defence genes (Klotz
et al
.,
2003; Luo
et al
., 2006) as well as to cause
the mitochondrial common deletion, which
is associated with skin photo-ageing
(Berneburg
et al
., 1999; Wertz
et al
., 2005).
Gene expression induced by UVA in
HaCaT keratinocytes is highly altered by
the presence of b-carotene, an effect that
was related to the suppression of
1
O
2
, as
well as with direct effects of b-carotene in
HaCaT cells (Wertz
et al
., 2005). Several
other workers have reported evidence of
the role of singlet oxygen in UVA photo-
induced damage (Krishna
et al
., 1991;
Halliwell
et al
., 1992; Sander
et al
., 2004).
Photodamage in DNA molecules induced
by endogenous and exogenous riboflavin
(vitamin B2) and derivatives were reported,
as well as the role of vitamin C acting as
an
1
O
2
suppressor (Cross
et al
., 1998;
Besaratinia
et al
., 2007).
Humans have several defence systems
to protect from photodamage, including a
small-molecule antioxidant present in the
intercellular compartments of korneocytes
and melanin, which is a biopolymer that effi-
ciently absorbs UV-VIS radiation as well as
being an efficient antioxidant agent (Krol
and Liebler, 1998; Callado, 2007) and also
generates singlet oxygen (Chiarelli-Neto
et al
., 2011). Even so, over-exposure to sun
can lead to several skin manifestations
including wrinkles, advance senescence of
dermal fibroblasts and epidermal keratino-
cytes, which eventually can lead to the
development of a cancer (Callado, 2007).
Clearly these effects are more pronounced in
less protected skins that have, among other
differences, lower amounts of melanin
(Slominski
et al
., 2004). Overproduction of
1
O
2
can lead to a human degenerative disease
called porphyria, caused by the accumula-
tion of porphyrins or porphyrin precursors
(Straka
et al
., 1990; Baptista, 1998). The
symptoms arise mostly from effects on the
nervous system and on the skin. Skin mani-
festations can include burning, blistering
and scarring of sun-exposed areas (Bickers
et al
., 2006).
The study of porphyria and its action
mechanisms have contributed significantly
to the development of therapies based on
photodynamic therapy (PDT). PDT is a
promising modality for the management of
various tumours and non-malignant dis-
eases, based on the combination of a photo-
sensitizer that is selectively localized in the
target tissue and illumination of the lesion
with visible light, resulting in photodamage
and subsequent cell death, which is mainly
due to singlet oxygen (Fattorusso, 1974;
Wilson
et al
., 1992; Kalka
et al
., 2000; Kessel,
2000; Tardivo
et al
., 2006). The photosensi-
tizer can also get involved in electron trans-
fer reactions, initiating radical-induced
damage in biomolecules (Baptista and Indig,
1998; Junqueira
et al
., 2002; Severino
et al
.,
2003). Although the initial PDT protocols
were very expensive and only performed in
a few hospitals with expensive laser sys-
tems, recently much attention has been paid
to developing inexpensive PDT protocols to
treat several diseases (Tardivo
et al
., 2006;
Tardivo and Baptista, 2009).
6.4
Chemical Reactivity
Singlet oxygen involvement in photo-
chemical reactions was first proposed by
Kautsky to explain sensitized oxidation of
substrates when absorbed on silica gel
(Fattorusso, 1974). It is an electrophilic spe-
cies, extremely reactive, that preferentially
attacks highly alkylated double bonds. In
biological systems,
1
O
2
attacks membranes,
proteins and nucleic acids. Its main reaction
route is addition to the double bonds,
although other reactions with specific targets
such as sulfur compounds are also possible
(Michaeli and Feitelson, 1994; Wilkinson
et al
., 1995). Singlet oxygen attacks alkenes
by three different mechanisms:
Formation of hydroperoxide (n-reac-
tion)
: This mechanism involves the forma-
tion of an allylic hydroperoxide, with a
concerted shift of the double bond. It is
likely that the intermediate involves a
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