Abstract
1. 1. The porphyrinogenic ability of several antineoplasics used in the therapy of the different cancers was evaluated. The action of cyclophosphamide, busulfan and 5-fluorouracil on the amount and nature of the accumulated hepatic porphyrins and on the activity of δ-aminolaevulinate synthase(ALA-S). were estimated at different doses and times of drug treatment in 17-day-old chick embryos. 2. 2. It was observed that cyclophosphamide produces a significant increase in the accumulation of hepatic porphyrins at different doses as well as in the activity of the ALA-S, at all the incubation times. Cyclophosphamide alters the pattern of porphyrins accumulated in the liver, where a coproporphyrin: protoporphyrin ratio higher than in the controls can be observed. 3. 3. Busulfan increased the hepatic porphyrins accumulated in the liver but to a lesser degree than cyclophosphamide. 4. 4. 5-Fluorouracil did not modify the hepatic porphyrin content when it was administered at doses up to 40 mg/embryo. 5. 5. When the embryos were injected with busulfan or 5-fluorouracil no significant differences were observed in the activity of ALA-S up to 11 hr of incubation. 6. 6. These results indicate that cyclophosphamide has a remarkable porphyrinogenic capacity in chick embryo while busulfan. notwithstancling the fact that it alters the haem pathway, it does so to a degree that does not impair the regulation of ALA-S activity. Fluorouracil seems to be non porphyrinogenic in this system, up to 40 mg/embryo.
Highlights
Porphyrias are metabolic disorders characterized by an increased excretion of porphyrins and/or their precursors and by the accumulation of porphyrins in some tissues
These results indicate that cyclophosphamide has a remarkable porphyrinogenic capacity in chick embryo while busulfan, notwithstanding the fact that it alters the haem pathway, it does so to a degree that does not impair the regulation of aminolaevulinate synthase (ALA-S) activity
Present results indicate that cyclophosphamide has a remarkable porphyrinogenic action in chick embryo, evidenced by an increase in ALA-S activity and a great accumulation of liver porphyrins (Figs 1. 2 and 5) that significantly modify its pattern as a consequence of drug treatment
Summary
Porphyrias are metabolic disorders characterized by an increased excretion of porphyrins and/or their precursors and by the accumulation of porphyrins in some tissues. The hepatic human porphyria cutanea tarda (PCT) is one of the most common forms of porphyria in which the disturbances of porphyrin metabolism are located mainly in liver (Meyer and Schmid, 1978). It is widely known that most PCT patients show a hepatic alteration with several degrees of severity. The high incidence of liver tumors in PCT is not merely related to hepatic cirrhosis (Soils et aL, 1982) and according to Rimbaud et al (1972). In these patients hepatic cirrhosis incidence is five times that found in the average population. Primary liver cancer is 100--200 times more frequent in PCT patients than in the rest of population (Kordac, 1972)
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