Rehana Rehman, Rakhshaan Khan, Muhammad Saleh Soomro, Muhammad Aslam Aslam


Background: A variety of stimuli cause a rapid increase in polyamine synthesis by increasing an
enzyme ornithine decarboxylase required for the biosynthetic pathway of protein synthesis. Difluoromethyl ornithine is a selective inhibitor of this enzyme and hence arrests cell replication
strikingly. Its effects on thyroid gland are studied with respect to change in animal’s weight and
levels of Triiodothyronine, Thyroxine and Thyroid stimulating hormone. The study was conducted
to evaluate the inhibitory effects of Di-fluoromethyl ornithine (DFMO) administration on
polyamine metabolism of thyroid gland in rats. Methods: The study was conducted on rats
weighing 248 to 320 grams, divided into control and DFMO treated group. A dose of 50 mg/rat
was administered subcutaneously to the treated group for 5 consecutive days and placebo (normal
saline) injections to control group. On sixth day, blood was collected by cardiac puncture and
serum was separated. Serum T3, T4 and TSH were analyzed with the help of radioimmunoassay in
both groups. Results: In treated group there was a fall in T3, T4 concentration with significant rise
in TSH concentration as compared to control group. Conclusion: DFMO (Difluoro methyl
ornithine) decreases cellular proliferation of thyroid gland as is assessed by decrease in thyroid
hormone levels. The hypothalamo pituitary thyroid axis however remains intact as is shown by a
feedback rise in TSH concentration. DFMO can thus be employed for anti-neoplastic clinical trials
on account of interference with activity of ODC (Ornithine Decarboxylase) fundamental for
polyamine biosynthesis.
Keywords: DFMO, ODC, thyroid, rats, radioimmunoassay


Metcalf BW, Bey P, Danzin C. Catalytic irreversible

inhibition of mammalian ornithine de-carboxylase by

substrate & product analogs. J. Am Chem Soc


Pegg AE. Recent advances in the biochemistry of polyamines

in eukaryotes. Biochem J 1986;234:249–62.

J Ayub Med Coll Abbottabad 2009;21(2)

http://www.ayubmed.edu.pk/JAMC/PAST/21-2/Rehana.pdf 89

Mamont PS, Bey P. Polyamines in Biochemical research (ed

Gaugas), London: John Wiley and Sons; 1980.p.147–66.

Crowell JA, Goldenthal EI. Chronic toxicity studies of the

potential cancer preventive 2-(Difluoromethyl)-dl-ornithine.

Fund Appl Toxicol 1994;22:341–54.

Heby O. Role of polyamines in the control of cell proliferation

& differentiation. Differentiation 1981;19(1):1–20

Pegg AE. Polyamine metabolism and its importance in

neoplastic growth and as a target for chemotherapy. Cancer

Res 1988;48:759–74.

Pegg AE, Mcgovern KA, Wiest L. Decarboxylation of α-

difluoromethylornithine 1987;241:305–7.

Ghoda L, Basu HS, Porter CW. Role of ornithine

decarboxylase suppression and polyamine depletion in the

antiproliferative activity of polyamine analogues Mol

Pharmacol 1992;42:302–6.

Tabor CW, Tabor H. Polyamines. Ann Rev Biochrm


Stoscheck CM, Erwin BG. Effect of inhibitors of ornithine

and S-adenosyl methionine decarboxylase on L6 myoblast

proliferation. J Cell Physiol 1982;110:161–8.

Creaven PJ, Pendyala L and Petrilli NJ.Evaluation of α-

difluoromethylornithine as a potential chemopreventive

agent: Tolerance to daily oral administration in

humans.Cancer Epidemiol Biomarkers Prev 1993;2:243–7.

Hill RN, Edrich LF. Review of Thyroid follicular cell

carcinogenesis. Fundam Appl Toxicol 1989;12:629–97.

Guyton AC. Thyroid metabolic hormones. In: Textbook of

Medical Physiology 8th Ed. Philadelphia: WB Saunders

Company;1991. p. 831.

Schulze Lohoff E,Brand K,Fees H.Role of ornithine

decarboxylase for proliferation of mesangial cells in culture.

Kidney Int 1991;40:684–90

Slotkin TA, Bartolome JL. Ornithine decarboxylase marker

of neuroendocrine & neurotransmitter actions. In: Methods in

Enzymology (Ed Conn) Vol.103. New York: Academic

press; (Part H)1983:590–6035.

Ask A, Persson L, Rehnholm A, Frostesjö L, Holm I, Heby

O. Development of resistance to hydroxyurea during

treatment of human myelogenous leukemia K562 cells with

alpha-difluoromethylornithine as a result of coamplification

of genes for ornithine decarboxylase and ribonucleotide

reductase R2 subunit. Cancer Res 1993;53:5262–8.

Aslam M, Nicholson S, Gillham B, Jones M.Permissive role

for ornithine decarboxylase and Putrescine in the leutizing

hormone surge. Neuroendocrinology 1987;45:473–8.

Leveque J,Foucher F,Moulinoux JP.Benefits of complete

polyamine depriviation in hormone responsive& hormone

resistant MCF-7human breast adenocarcinoma in vivo

Anticancer Res 2000;20:97–101.

Terzis J, Pederson PH, Feuerstein BG, Arnold H. Effect of

DFMO on glial cell proliferation,migration & invasion in

vitro. J Neurooncol.1998;36:113–21.

Rehana R, Lubna F, Aslam M. Effect of Putrescine on

Thyroid function in rats. Pak Armed Forces Med J


Seiler N,Atanassov CL,Raul F. Polyamine metabolism as

target for cancer chemo-prevention(Review) Int J


Pegg AE. Polyamine metabolism and its importance in

neoplstic growth and a target for chemotherapy. Cancer Res


Pegg AE, Shantz LM, Coleman CS. Ornithine decarboxylase

as a target for chemoprevention. J Cell Biochem Suppl


Marton LJ, Pegg AE. Polyamines as targets for therapeutic

intervention. Annu Rev Pharmacol Toxicol 1995;35:55–91.


  • There are currently no refbacks.

Contact Number: +92-992-382571

email: [jamc] [@] [ayubmed.edu.pk]