Deoxycoformycin toxicity in mice after long-term treatment

Ram P. Agarwal

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Deoxycoformycin, a tight-binding inhibitor of the enzyme adenosine deaminase, is a potent lymphocytotoxic agent. To examine the effect of deoxycoformycin on mouse tissues the drug was administered IP either by single or by repeated injections at one of two dose levels (0.2 or 10.0 mg/kg). Treatment with repeated injections at the higher dose caused retardation of growth and increases in lung and splenic mass. Body temperature, hematocrit, and total leukocyte count remained constant. Single injections at the lower dose caused complete inhibition of adenosine deaminase in liver and blood, and partial inhibition in jejunum and spleen, but at the higher dose complete inhibition of the enzyme in all tissues was obtained. Dosage appeared to have no effect on the rate of recovery of the deoxycoformycin-inhibited enzyme but marked tissue differences were observed. The enzymic activity recovered rapidly in jejunum (100% in 1 day) but slowly in other tissues (after 28 days, about 60% in spleen and liver; about 85% in kidney and blood, and 100% in lungs). These observations suggest that the recovery of inhibited enzyme depends largely upon the rate of proliferation of cells and protein synthesis. These tissue differences in recovery rates may play a role in the pharmacological and chemotherapeutic behavior of this drug.

Original languageEnglish
Pages (from-to)83-87
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume5
Issue number2
DOIs
StatePublished - Dec 1 1980
Externally publishedYes

Fingerprint

Pentostatin
Toxicity
Tissue
Adenosine Deaminase
Jejunum
Recovery
Liver
Injections
Blood
Enzymes
Spleen
Adenosine Deaminase Inhibitors
Therapeutics
Lung
Enzyme Inhibitors
Body Temperature
Leukocyte Count
Hematocrit
Pharmaceutical Preparations
Cell Proliferation

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

Cite this

Deoxycoformycin toxicity in mice after long-term treatment. / Agarwal, Ram P.

In: Cancer Chemotherapy and Pharmacology, Vol. 5, No. 2, 01.12.1980, p. 83-87.

Research output: Contribution to journalArticle

@article{5691a81d54104d428407ae6a0ab1cb4b,
title = "Deoxycoformycin toxicity in mice after long-term treatment",
abstract = "Deoxycoformycin, a tight-binding inhibitor of the enzyme adenosine deaminase, is a potent lymphocytotoxic agent. To examine the effect of deoxycoformycin on mouse tissues the drug was administered IP either by single or by repeated injections at one of two dose levels (0.2 or 10.0 mg/kg). Treatment with repeated injections at the higher dose caused retardation of growth and increases in lung and splenic mass. Body temperature, hematocrit, and total leukocyte count remained constant. Single injections at the lower dose caused complete inhibition of adenosine deaminase in liver and blood, and partial inhibition in jejunum and spleen, but at the higher dose complete inhibition of the enzyme in all tissues was obtained. Dosage appeared to have no effect on the rate of recovery of the deoxycoformycin-inhibited enzyme but marked tissue differences were observed. The enzymic activity recovered rapidly in jejunum (100{\%} in 1 day) but slowly in other tissues (after 28 days, about 60{\%} in spleen and liver; about 85{\%} in kidney and blood, and 100{\%} in lungs). These observations suggest that the recovery of inhibited enzyme depends largely upon the rate of proliferation of cells and protein synthesis. These tissue differences in recovery rates may play a role in the pharmacological and chemotherapeutic behavior of this drug.",
author = "Agarwal, {Ram P.}",
year = "1980",
month = "12",
day = "1",
doi = "10.1007/BF00435409",
language = "English",
volume = "5",
pages = "83--87",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - Deoxycoformycin toxicity in mice after long-term treatment

AU - Agarwal, Ram P.

PY - 1980/12/1

Y1 - 1980/12/1

N2 - Deoxycoformycin, a tight-binding inhibitor of the enzyme adenosine deaminase, is a potent lymphocytotoxic agent. To examine the effect of deoxycoformycin on mouse tissues the drug was administered IP either by single or by repeated injections at one of two dose levels (0.2 or 10.0 mg/kg). Treatment with repeated injections at the higher dose caused retardation of growth and increases in lung and splenic mass. Body temperature, hematocrit, and total leukocyte count remained constant. Single injections at the lower dose caused complete inhibition of adenosine deaminase in liver and blood, and partial inhibition in jejunum and spleen, but at the higher dose complete inhibition of the enzyme in all tissues was obtained. Dosage appeared to have no effect on the rate of recovery of the deoxycoformycin-inhibited enzyme but marked tissue differences were observed. The enzymic activity recovered rapidly in jejunum (100% in 1 day) but slowly in other tissues (after 28 days, about 60% in spleen and liver; about 85% in kidney and blood, and 100% in lungs). These observations suggest that the recovery of inhibited enzyme depends largely upon the rate of proliferation of cells and protein synthesis. These tissue differences in recovery rates may play a role in the pharmacological and chemotherapeutic behavior of this drug.

AB - Deoxycoformycin, a tight-binding inhibitor of the enzyme adenosine deaminase, is a potent lymphocytotoxic agent. To examine the effect of deoxycoformycin on mouse tissues the drug was administered IP either by single or by repeated injections at one of two dose levels (0.2 or 10.0 mg/kg). Treatment with repeated injections at the higher dose caused retardation of growth and increases in lung and splenic mass. Body temperature, hematocrit, and total leukocyte count remained constant. Single injections at the lower dose caused complete inhibition of adenosine deaminase in liver and blood, and partial inhibition in jejunum and spleen, but at the higher dose complete inhibition of the enzyme in all tissues was obtained. Dosage appeared to have no effect on the rate of recovery of the deoxycoformycin-inhibited enzyme but marked tissue differences were observed. The enzymic activity recovered rapidly in jejunum (100% in 1 day) but slowly in other tissues (after 28 days, about 60% in spleen and liver; about 85% in kidney and blood, and 100% in lungs). These observations suggest that the recovery of inhibited enzyme depends largely upon the rate of proliferation of cells and protein synthesis. These tissue differences in recovery rates may play a role in the pharmacological and chemotherapeutic behavior of this drug.

UR - http://www.scopus.com/inward/record.url?scp=0019132706&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0019132706&partnerID=8YFLogxK

U2 - 10.1007/BF00435409

DO - 10.1007/BF00435409

M3 - Article

VL - 5

SP - 83

EP - 87

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 2

ER -