In previous work we found a 30% increase in the effectiveness of the photodynamic treatment of
cancer when combined with the administration of
cyclophosphamide (CPM). Here we have tried to elucidate the mechanism responsible for such potentiation. Male Balb/C mice bearing a transplantable
adenocarcinoma were given 2 or 3 doses of 150 mg of CPM/kg weight intraperitoneally. At 16 and 40 hrs. after the last injection the animals were sacrificed.
Tumor and liver were excised and 5-aminolevulinic
acid dehydratase and
porphobilinogen deaminase activities were determined. Intracellular levels of
glutathione and
cytochrome P450 were also measured. A 15 to 30% decrease in liver 5-aminolevulinic
acid dehydratase activity was observed 40 hrs. after the last injection. The
tumor enzyme was 30 to 40% inhibited. The activity of liver
porphobilinogen deaminase in CPM treated mice decreased to a minimum (15% below the control) at 16 hrs. after administration of the
drug and in
tumors a decrease of 20% was shown 40 hrs. post CPM injection. The greater the number of CPM doses administered the higher the decrease in the enzymatic activities. CPM treatment did not change total
tumor glutathione levels but the reduced/
oxidized glutathione ratio was significantly modified in the tumoral tissue.
Cytochrome P450 levels were not increased. These data indicate that CPM-induced potentiation of the photodynamic damage of tumoral tissue is mediated by a mechanism other than that of increased
porphyrin synthesis.