Evaluation of the Porphyrinogenic Risk of Antineoplastics

• Published in: Journal of applied toxicology Vol. 17; no. 3; pp. 171 - 177
• Main Authors: Cochón, Adriana Cristina, Aldonatti, Carmen, Carmen San Martín de Viale, Leonor, Wainstok de Calmanovici, Rosa
• Format: Journal Article
• Language: English
• Published: Chichester John Wiley & Sons, Ltd 01-05-1997; Wiley
• Subjects: Alkylating Agents - toxicity; Altretamine - toxicity; Animals; Antineoplastic Agents - adverse effects; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; antineoplastics; Azathioprine - toxicity; Biological and medical sciences; Busulfan - toxicity; Chick Embryo; Cyclophosphamide - adverse effects; Cyclophosphamide - chemistry; Cyclophosphamide - toxicity; Dacarbazine - toxicity; Dicarbethoxydihydrocollidine - toxicity; Drug toxicity and drugs side effects treatment; Female; ferrochelatase; Ferrochelatase - drug effects; Ferrochelatase - metabolism; Flavoproteins; Fluorouracil - toxicity; Liver - drug effects; Liver - metabolism; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mitochondrial Proteins; Oxidoreductases - drug effects; Oxidoreductases - metabolism; Oxidoreductases Acting on CH-CH Group Donors; Pharmacology. Drug treatments; porphyria; Porphyrias - chemically induced; porphyrins; Porphyrins - metabolism; Procarbazine - toxicity; Protoporphyrinogen Oxidase; Structure-Activity Relationship; Toxicity: skin, dermoskeleton; δ-aminolaevulinic acid synthase; Antineoplastic agent; Porphyria; Procarbazine; Skin disease; Embryo; Toxicity; Liver; Lyases; Chlorambucil; Dacarbazine; Enzymatic activity; Risk assessment; Melphalan; Altretamine; Busulfan; Aves; Fluorouracil; Acyltransferases; Enzyme; Ferrochelatase; Transferases; Rodentia; 5-Aminolevulinate synthase; Genetic disease; Vertebrata; Cyclophosphamide; Mammalia; Mouse; Porphyrin; Animal; Protoporphyrinogen oxidase; Chicken; Oxidoreductases; Biological accumulation; Azathioprine
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/(SICI)1099-1263(199705)17:3<171::AID-JAT419>3.0.CO;2-A

The use of antineoplastics is common in cancer therapy, and some of them have been associated with the development of porphyria in patients with cancer. However, knowledge of their effects on the haeme metabolic pathway is at present scarce and unclear. So, the present study evaluates the porphyrinogenic ability of nine antineoplastics (both alkylating and non‐alkylating). These were tested either alone or in conjunction with 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (latent porphyria model) in chick embryos and in mice. The results obtained suggest that the use of cyclophosphamide, azathioprine, 5‐fluorouracil, busulphan, procarbazine and hexamethylmelamine be avoided in the treatment of porphyric patients. On the other hand, dacarbazine, chlorambucil and melphalan are non‐porphyrinogenic. We also provide evidence showing that neither the presence of the mustard group in the structure of the antineoplastic nor alterations in ferrochelatase or protoporphyrinogen oxidase activities are responsible for the porphyrinogenic ability of cyclophosphamide. © 1997 by John Wiley & Sons, Ltd.