Evaluation of the porphyrinogenic risk of antineoplastics.
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.
Cochón
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AC
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Aldonatti
C
C
San Martín de Viale
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LC
Wainstok de Calmanovici
R
R
D000477:Alkylating Agents / Q000633:toxicity; D006585:Altretamine / Q000633:toxicity; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000633:toxicity*; D001379:Azathioprine / Q000633:toxicity; D002066:Busulfan / Q000633:toxicity; D002642:Chick Embryo; D003520:Cyclophosphamide / Q000009:adverse effects / Q000737:chemistry / Q000633:toxicity; D003606:Dacarbazine / Q000633:toxicity; D003997:Dicarbethoxydihydrocollidine / Q000633:toxicity*; D005260:Female; D005294:Ferrochelatase / Q000187:drug effects / Q000378:metabolism; D005420:Flavoproteins; D005472:Fluorouracil / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D024101:Mitochondrial Proteins; D010088:Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011164:Porphyrias / Q000139:chemically induced*; D011166:Porphyrins / Q000378:metabolism; D011344:Procarbazine / Q000633:toxicity; D050768:Protoporphyrinogen Oxidase; D013329:Structure-Activity Relationship
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D005420:Flavoproteins; D024101:Mitochondrial Proteins; D011166:Porphyrins; D011344:Procarbazine; D003997:Dicarbethoxydihydrocollidine; D003606:Dacarbazine; D003520:Cyclophosphamide; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C493979:Ppox protein, mouse; D050768:Protoporphyrinogen Oxidase; D005294:Ferrochelatase; D002066:Busulfan; D001379:Azathioprine; D006585:Altretamine; D005472:Fluorouracil