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The treatment focuses on combined treatment with ALA and Oph in a murine
syngeneic solid tumor model using Meth-A cells. It was shown that the combination
of ALA and Oph induced the accumulation of porphyrins in Met- A cells and upon
exposure to light, significantly reduced the surface area of the tumors and induces
their destruction, as determined by their disappearance at both the visual and
histological levels. These data supported the possibility that the accumulation of
Proto and subsequent photodestruction of tumor cells can be significantly enhanced
in vivo by the use of joint AlA an tetrapyrrole modulator
19.5.1 Proto Accumulation in ALA and Oph Treated
Meth-A Ascites Cell Suspensions
We determined whether treatment of Meth-A cells in vitro with ALA and Oph
would result in Proto accumulation. Meth-A ascites cells were treated with 1 mM
ALA and 0.75 mM Oph for 3.5 h in darkness. The combination of ALA and Oph
induced very significant increases in Proto accumulation (338 nmol/100 mg pro-
tein; P
0.05). Treatment with ALA alone also induced measurable accumulation
of Proto (61.73 nmol/100 mg protein) in comparison with control cells, but this was
not statistically significant (Rebeiz et al. 1996b ). This level of Proto accumulation is
approximately six fold lower than the levels that accumulate with ALA + Oph
treatment. This finding is also consistent with the specific cell lysis data in which
ALA + Oph-induced cell lysis was approximately seven times higher than that
arising from treatment with ALA alone (Rebeiz et al. 1996b ). It is interesting that
the addition of Oph to ALA-treated Meth-A cells induced more Proto accumulation
than what was seen previously in MLA 144 cells (Rebeiz et al. 1992 ). Therefore it
was concluded that some cell type specificity was observed because the efficacy of
ALA and Oph in stimulating Proto accumulation appeared to vary significantly
with cell types.
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19.5.2 Sensitivity of Meth-A Cells to ALA and Oph
Treatment
Since previous results had shown a positive correlation between the amount of
Proto accumulation and specific cell lysis upon illumination in several transformed
cell lines treated with ALA and Oph (Rebeiz et al. 1992 ), Meth-A cells were
screened for sensitivity to light activated cell lysis after ALA and Oph treatment.
There was no apparent cell lysis in darkness (3 h) in Meth-A cells in medium, or
in cells treated with I mM ALA or 0.75 mM Oph alone (Rebeiz et al. 1996b ).
However, there was an increase in cell lysis when cells were treated with both
compounds in darkness ( P
0.05) then were exposed to light. Indeed, upon light
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