EFFICACY OF
PREVENTIVE PROSTAGLANDIN TREATMENT OF MAMMARY
LESIONS, IN RATS: AN EXPERIMENTAL TRIAL
ARNE N. GJORGOV, M.D., PH.D.,
THAMRADEEN A. JUNAID, M.D., FRCP, Professor of
Histopathology,
GARY R. BURNS, B.SC., PH.D., Associate Professor
of Biochemistry,
LABIBA TEMMIM, M.D., M.B.HUM., and GRACY ALEX,
M.B.B.C.
Department of Community Medicine and Department
of Pathology, Faculty of Medicine,
Kuwait University, and the Kuwait Cancer
Control Center, Kuwait
The aim
of the study was to assess the efficacy of the preventive prostaglandin
(PG) treatment in prevention of spontaneous tumors of mammary glands and
other organs of female reproductive and related systems in small animals
by creating a controlled environment to the laboratory animals which would
reflect the actual exposure in the development of breast tumors in human
females, with no extraneous, chemical, toxicological, hormonal or physical
factors; to test the postulated cause-and-effect relation of the lack of
seminal factors, presumably the Prostaglandins, in the tumorigenesis of
mammary glands and other reproductive organs in female rats; to quantify
the neoplastic effects in the female rats, exposed to six different reproductive
conditions, and treatment and control procedures; and to test a set of
15 defined, interrelated hypotheses. An extended control-group time-series
laboratory experiment on Wistar rats was performed. A colony of 300 female
and 110 male animals, randomly allocated into six groups of 50 females,
and housed together with 18 male animals of controlled and differentiated
reproductive capacity. The tumorigenesis in the female rats was induced
by sterile mating with vasectomized male animals only. Females were exposed
to different reproductive potentials, such as male and female sterility,
normal pregnancy, pseudopregnancy, preventive treatment with Prostaglandins
of two-level dosage regimen, and a PG-vehicle, placebo maneuver. The observation
period lasted one year. Spontaneous neoplastic lesions, palpable and histopathologically
evaluated after sacrifice of the animals, carried out by two qualified
ratters (histopathologists), in aggregates and incidence rates, of the
target organs: mammary glands, ovaries, uterus, thyroid, adrenals, pituitary.
Two hundred and nineteen female rats, out of the 296, survived the 13 months
of observation. The first palpable mammary nodules were found in females
exposed to vasectomized males (Group 1) in less than one month. The incidence
of histopathologically confirmed mammary lesions was highest in this vesectomy-exposed
female rats, with a rate of 89.5 percent, followed by the incidence in
the PG-vehicle, placebo-treated female rats (Group 6), with a rate of 57.6%.
Several cases of inordinate, circling, fatal conditions, first occurring
in the 3rd month of observation, were observed in female rats of groups
(1) and (6), with an estimated 7% incidence rate of the condition. The
lowest incidence of mammary lesions, 18.9%, was found in the PG-treated
females (of Groups 4 and 5), as expected, along with the incidence of 20.7%
in fertile females of the control group exposed to intact males (Group
2) and an incidence of 32.3% in the infertile, tubo-ligated females exposed
to intact males (Group 3). The differences to the baseline Group 1 were
statistically significant (p<.0001). The ovarian and uterine lesions
reached the highest incidence of almost 100% in the vasectomy-exposed group.
The lowest incidence of pelvic lesions was found in the control animals
(Group 2), exposed to perpetuate pregnancies, multiple deliveries, and
21-day breast-feedings. No dose-effect relation was found in the PG preventive
interventions on any lesions. The Kappa value showed fair to good agreement
beyond chance between the two ratters for the mammary lesions. The results
of the experimental study supported the research hypothesis of a preventive
potential of certain seminal factors, the Prostaglandins, against the development
of neoplastic lesions in mammary glands and other reproductive and endocrine
organs, in small animals. The efficacy of the PG-treatment was estimated
at 73.7% in the prevention of mammary lesions (p<.0001). The efficacy
of the preventive PG treatment was found to exhibit significant preventive
effects on ovarian (45%) and thyroid lesions (90%) as well.
Present address:
Arne N. Gjorgov, M.D., Ph.D.,
MEDICS Group,
G. Hadzi-Panzov Street, No. 2,
Skopje,
Republic of Macedonia.
Phone & fax:
+389-91-127 361.