title: Effect of some antineoplastics on metabolic heme pathway.
abstract: 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.
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaira, Argentina.
authors.forename: R
authors.initials: R
authors.lastname: Wainstok de Calmanovici
authors.forename: L C
authors.initials: LC
authors.lastname: San Martín de Viale
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D011166:Porphyrins; D006418:Heme; D003520:Cyclophosphamide; D000624:5-Aminolevulinate Synthetase; D002066:Busulfan; D005472:Fluorouracil