Metabolic changes in the heme pathway driven by cyclophosphamide treatment in mice.
In previous work we found a 30% increase in the effectiveness of the photodynamic treatment of cancer when combined with the administration of cyclophosphamide (CPM). Here we have tried to elucidate the mechanism responsible for such potentiation. Male Balb/C mice bearing a transplantable adenocarci...
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1997
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01455680_v43_n1_p95_Casas http://hdl.handle.net/20.500.12110/paper_01455680_v43_n1_p95_Casas |
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paper:paper_01455680_v43_n1_p95_Casas2023-06-08T15:12:22Z Metabolic changes in the heme pathway driven by cyclophosphamide treatment in mice. Casas, Adriana Gabriela Fukuda, Haydeé Batlle, Alcira María del Carmen alkylating agent cyclophosphamide cytochrome P450 glutathione heme porphobilinogen deaminase porphobilinogen synthase animal article Bagg albino mouse male metabolism mouse Animals Antineoplastic Agents, Alkylating Cyclophosphamide Cytochrome P-450 Enzyme System Glutathione Heme Hydroxymethylbilane Synthase Male Mice Mice, Inbred BALB C Porphobilinogen Synthase In previous work we found a 30% increase in the effectiveness of the photodynamic treatment of cancer when combined with the administration of cyclophosphamide (CPM). Here we have tried to elucidate the mechanism responsible for such potentiation. Male Balb/C mice bearing a transplantable adenocarcinoma were given 2 or 3 doses of 150 mg of CPM/kg weight intraperitoneally. At 16 and 40 hrs. after the last injection the animals were sacrificed. Tumor and liver were excised and 5-aminolevulinic acid dehydratase and porphobilinogen deaminase activities were determined. Intracellular levels of glutathione and cytochrome P450 were also measured. A 15 to 30% decrease in liver 5-aminolevulinic acid dehydratase activity was observed 40 hrs. after the last injection. The tumor enzyme was 30 to 40% inhibited. The activity of liver porphobilinogen deaminase in CPM treated mice decreased to a minimum (15% below the control) at 16 hrs. after administration of the drug and in tumors a decrease of 20% was shown 40 hrs. post CPM injection. The greater the number of CPM doses administered the higher the decrease in the enzymatic activities. CPM treatment did not change total tumor glutathione levels but the reduced/oxidized glutathione ratio was significantly modified in the tumoral tissue. Cytochrome P450 levels were not increased. These data indicate that CPM-induced potentiation of the photodynamic damage of tumoral tissue is mediated by a mechanism other than that of increased porphyrin synthesis. Fil:Casas, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fukuda, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Del C Batlle, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 1997 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01455680_v43_n1_p95_Casas http://hdl.handle.net/20.500.12110/paper_01455680_v43_n1_p95_Casas |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
alkylating agent cyclophosphamide cytochrome P450 glutathione heme porphobilinogen deaminase porphobilinogen synthase animal article Bagg albino mouse male metabolism mouse Animals Antineoplastic Agents, Alkylating Cyclophosphamide Cytochrome P-450 Enzyme System Glutathione Heme Hydroxymethylbilane Synthase Male Mice Mice, Inbred BALB C Porphobilinogen Synthase |
| spellingShingle |
alkylating agent cyclophosphamide cytochrome P450 glutathione heme porphobilinogen deaminase porphobilinogen synthase animal article Bagg albino mouse male metabolism mouse Animals Antineoplastic Agents, Alkylating Cyclophosphamide Cytochrome P-450 Enzyme System Glutathione Heme Hydroxymethylbilane Synthase Male Mice Mice, Inbred BALB C Porphobilinogen Synthase Casas, Adriana Gabriela Fukuda, Haydeé Batlle, Alcira María del Carmen Metabolic changes in the heme pathway driven by cyclophosphamide treatment in mice. |
| topic_facet |
alkylating agent cyclophosphamide cytochrome P450 glutathione heme porphobilinogen deaminase porphobilinogen synthase animal article Bagg albino mouse male metabolism mouse Animals Antineoplastic Agents, Alkylating Cyclophosphamide Cytochrome P-450 Enzyme System Glutathione Heme Hydroxymethylbilane Synthase Male Mice Mice, Inbred BALB C Porphobilinogen Synthase |
| description |
In previous work we found a 30% increase in the effectiveness of the photodynamic treatment of cancer when combined with the administration of cyclophosphamide (CPM). Here we have tried to elucidate the mechanism responsible for such potentiation. Male Balb/C mice bearing a transplantable adenocarcinoma were given 2 or 3 doses of 150 mg of CPM/kg weight intraperitoneally. At 16 and 40 hrs. after the last injection the animals were sacrificed. Tumor and liver were excised and 5-aminolevulinic acid dehydratase and porphobilinogen deaminase activities were determined. Intracellular levels of glutathione and cytochrome P450 were also measured. A 15 to 30% decrease in liver 5-aminolevulinic acid dehydratase activity was observed 40 hrs. after the last injection. The tumor enzyme was 30 to 40% inhibited. The activity of liver porphobilinogen deaminase in CPM treated mice decreased to a minimum (15% below the control) at 16 hrs. after administration of the drug and in tumors a decrease of 20% was shown 40 hrs. post CPM injection. The greater the number of CPM doses administered the higher the decrease in the enzymatic activities. CPM treatment did not change total tumor glutathione levels but the reduced/oxidized glutathione ratio was significantly modified in the tumoral tissue. Cytochrome P450 levels were not increased. These data indicate that CPM-induced potentiation of the photodynamic damage of tumoral tissue is mediated by a mechanism other than that of increased porphyrin synthesis. |
| author |
Casas, Adriana Gabriela Fukuda, Haydeé Batlle, Alcira María del Carmen |
| author_facet |
Casas, Adriana Gabriela Fukuda, Haydeé Batlle, Alcira María del Carmen |
| author_sort |
Casas, Adriana Gabriela |
| title |
Metabolic changes in the heme pathway driven by cyclophosphamide treatment in mice. |
| title_short |
Metabolic changes in the heme pathway driven by cyclophosphamide treatment in mice. |
| title_full |
Metabolic changes in the heme pathway driven by cyclophosphamide treatment in mice. |
| title_fullStr |
Metabolic changes in the heme pathway driven by cyclophosphamide treatment in mice. |
| title_full_unstemmed |
Metabolic changes in the heme pathway driven by cyclophosphamide treatment in mice. |
| title_sort |
metabolic changes in the heme pathway driven by cyclophosphamide treatment in mice. |
| publishDate |
1997 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01455680_v43_n1_p95_Casas http://hdl.handle.net/20.500.12110/paper_01455680_v43_n1_p95_Casas |
| work_keys_str_mv |
AT casasadrianagabriela metabolicchangesinthehemepathwaydrivenbycyclophosphamidetreatmentinmice AT fukudahaydee metabolicchangesinthehemepathwaydrivenbycyclophosphamidetreatmentinmice AT batllealciramariadelcarmen metabolicchangesinthehemepathwaydrivenbycyclophosphamidetreatmentinmice |
| _version_ |
1768545044302659584 |