Effect of some antineoplastics on metabolic heme pathway.
1. The porphyrinogenic ability of several antineoplastics 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 delta-aminolaevulinate synthase (ALA-S), were estimated at different doses and times of drug treatment in 17-day-old chick embryos. 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. Busulfan increased the hepatic porphyrins accumulated in the liver but to a lesser degree than cyclophosphamide. 4. 5-Fluorouracil did not modify the hepatic porphyrin content when it was administered at doses up to 40 mg/embryo. 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. 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 ALA-S activity. Fluorouracil seems to be non porphyrinogenic in this system, up to 40 mg/embryo.
Wainstok de Calmanovici
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Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaira, Argentina.
San Martín de Viale
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D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002066:Busulfan / Q000494:pharmacology; D002642:Chick Embryo; D003520:Cyclophosphamide / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D006418:Heme / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D011166:Porphyrins / Q000378:metabolism
D000970:Antineoplastic Agents; D011166:Porphyrins; D006418:Heme; D003520:Cyclophosphamide; D000624:5-Aminolevulinate Synthetase; D002066:Busulfan; D005472:Fluorouracil