Effect of some antineoplasics on metabolic heme pathway

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. © 1988.Fil:Wainstok De Calmanovici, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:San Martin De Viale, L.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Liver porphyrinogen carboxylyase in hexachlorobenzene porphyric rats. Studies with intermediate porphyrinogens of series III and with uroporphyrinogen I

1. 1. The present work studies the action of hexachlorobenzene (HCB) on the decarboxylation of uroporphyrinogen (Urogen) I and III and also on the decarboxylation of intermediate porphyrinogens of series III under different conditions using liver of normal and porphyric rats as enzyme source. 2. 2. The same enzyme is involved in the Urogen decarboxylation of both isomeric series I and III and catalyses the four steps in both cases. HCB affects all of them. 3. 3. HCB blocks the four steps of Urogen III decarboxylation to the same degree, as a function of intoxication time. 4. 4. HCB leads, in general, to an increase in the efficiency (Km/Vmax) of the porphyric system. These data can be interpreted as a reaction of the organism to overcome the enzymatic blockade. © 1987.Fil:Rios de Molina del, M.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Wainstok de Calmanovici, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:San Martin de Viale, L.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Influence of the strain of rats on the induction of hexachlorobenzene induced porphyria

1. 1. The present work undertakes a comparative study on the hexachlorobenzene (HCB) porphyria induction in female rats of Wistar and CHBBTHOM strains. The purpose was to characterize the CHBBTHOM strain with respect to the haem metabolic pathway, its regulatory mechanisms and its response to foreign drugs. 2. 2. After 7 weeks of treatment it was observed that the hepatic porphyrins increased 140 times, ALA-synthase 4 times and PCL was 73% inhibited in the Wistar strain. 3. 3. On the other hand the animals of CHBBTHOM strain showed lesser alteration on these parameters; hepatic porphyrins increased only 3-fold, ALA-synthase 1.7-fold and PCL was only 22% inhibited. 4. 4. Total iron liver content was nearly equal in both strains of rats. 5. 5. The results obtained would indicate that the lower susceptibility of the CHBBTHOM strain to acquire porphyria does not seem to be due to either: (1) congenital alterations of any parameters of the haem metabolic pathway, since the behaviour of normal animals from both strains was similar; or (2) a lower hepatic iron content in such animals. 6. 6. These findings would suggest that the differential response to HCB to this strain would be looked for in another metabolic pathway, such as that involved in the metabolization process of the toxic. © 1989.Fil:Wainstok de Calmanovici, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:Billi de Catabbi, S.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.Fil:San Martin de Viale, L.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina