Abstract
The effect of the cytostatics doxorubicin, 6-thioguanine and cytarabine on retinol store in rat liver was examined. When rats were treated with pharmacological doses of the combination of doxorubicin and 6-thioguanine for 10 days, the content of retinol in the liver was reduced by about 33%. In a longer term experiment, doxorubicin and cytarabine given separately reduced the retinol store by 33% and 11%, respectively, while doxorubicin and 6-thioguanine given in combination reduced retinol in liver by 31%. For one of the cytostatics (doxorubicin) the effects on plasma retinol and on acyl CoA:retinol acyltransferase (ARAT) activity in small intestine were also examined. Both were transiently reduced during the experiment.
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Abbreviations
- ASAT:
-
aspartate amino transferase
- ALAT:
-
alanine amino transferase
- HPLC:
-
high performance liquid chromatography
- AML:
-
acute myeloid leukemia
- RBP:
-
retinol-binding protein
- DTT:
-
dithiothreitol
- DMSO:
-
dimethylsulphoxide
- DPPD:
-
N-N-diphenyl-p-phenylendiamine
- WCC:
-
white cell count
- DDT:
-
dichloro-diphenyltrichloroethane
- TCDD:
-
2, 3, 7, 8-tetrachlorodibenzo-p-dioxin
- ARAT:
-
acyl CoA: retinol acyltransferase
References
Roberts A B, Sporn M B: Cellular biology and biochemistry of the retinoids, in Sporn M B, Roberts A B and Goodman D S (eds):The Retinoids, Vol. 2, pp. 210–286. Orlando, Academic Press (1984).
Strickland S, Mahdavi V: The induction of differentiation in teratocarcinoma stem cells by retinoic acid.Cell 15, 393 (1978).
Breitman T, Selonick S, Collins S: Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid.Proc natn Acad Sci USA 77, 2936 (1980).
Moon R, Itri L: Retinoids and Cancer, in Sporn M B, Roberts A B and Goodman D S (eds):The Retinoids, Vol. 2, pp. 327–371. Orlando, Academic Press (1984).
Goodman D S: Vitamin A and retinoids in health and disease.New Engl J Med 310, 1023 (1984).
Chessells J M: Acute leukaemias in children, in Gale R P and Hoffbrand A V (eds):Clinics in Haematology, Vol. 15, pp. 727–753. Philadelphia, W. B. Saunders (1986).
Creutzig U, Ritter J, Riehm H, Langermann H, Henze G, Kabisch H, Niethammer D, Jurgens H, Stollmann B, Lasson U, Kaufmann U, Loffler H, Schellong G: Improved treatment results in childhood acute myelogenous leukemia: a report of the German cooperative study AML-BFM-78.Blood 65, 298 (1985).
Sato M, Lieber C: Hepatic vitamin A depletion after chronic ethanol consumption in baboons and rats.J Nutr 111, 2015 (1981).
Underwood B: Vitamin A in animal and human nutrition, in Sporn M B, Roberts A B and Goodman D S (eds):The Retinoids, Vol. 1, pp. 282–392. Orlando, Academic Press (1984).
Leo M, Lowe N, Lieber C: Decreased hepatic vitamin A after drug administration in men and in rats.Am J clin Nutr 40, 1131 (1984).
Freireich E, Gehan E, Rall D, Schmidt L, Skipper H: Quantitative comparison of toxicity of anticancer agents in mouse, rat, hamster, dog, monkey, and man.Cancer Chemother Rep 50, 219 (1966).
Rasmussen M, Petersen L B, Norum K R: The activity of acyl CoA: retinol acyltransferase in the rat: variation with vitamin A status.Br J Nutr 51, 245 (1984).
Lowry O, Rosebrough N, Farr A, Randall R: Protein measurement with the folin phenol reagent.J biol Chem 193, 265 (1951).
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Wathne, KO., Blomhoff, R. & Norum, K.R. Effect of cytostatics on liver retinol store in rat. Med. Oncol. & Tumor Pharmacother. 5, 107–112 (1988). https://doi.org/10.1007/BF02985447
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DOI: https://doi.org/10.1007/BF02985447