studia universitatis babeş-bolyai biologia 2

C. PAŞCA et al.
Cisplatin (Platinol, cis-DDP) is a platinum compound belonging to the
alkylating agents, successfully applied in the chemotherapy of several types of
cancer. The antineoplasic activity is generally believed to result from the
interaction of the drug with the DNA in the tumour cells, this interaction leading to
the formation of different types of adducts through the reaction of the bifunctional
platinum compound with N7 atoms of the nucleobases guanine and adenine. The
major adducts are intrastrand cross-links formed by the binding of cis-DDP on two
neighbouring guanines, on adenine and guanine, and on two guanines separated by
one or more nucleobases. Other types of adducts formed are the interstrand crosslink
on two guanines and monofunctionally bound cis-DDP. Inside cells, cis-DDP
can form DNA-protein cross-links [6-8]. Cisplatin has a significant hematologic
and nonhematologic toxicity, especially nephrotoxicity. The histological and
ultrastructural modifications induced by this anticancer drug on the rat kidney are
still incompletely known; therefore, our investigations tried to emphasise these aspects
in concordance with the moment of the sacrification after the administration of
some therapeutic doses.
Material and methods. Our experiments were carried out with the following
five groups of healthy adult male Wistar rats, weighing 190 + 10 g and maintained
under bioclimatic laboratory conditions, with no food for 18 hours before the
treatment, but having water ad libitum:
-group U – untreated (control) group;
-group C 1 , C 2 , C 3 and C 4 treated i.v. with 20 mg Cisplatin /m 2 body surface/day,
for three days, and sacrificed 24 hours, 4, 11 and 18 days after the treatment.
The animals were not fed for 18 hours before the sacrification. Having
sacrificed the animals, we took fragments from the kidney. For microscopic
examination the fragments were fixed in 10% neutral formol, processed by the
paraffin technique and the sections of 6 µm were stained by the hematoxylin-eosin,
Masson-Goldner trichrome and PAS methods [12]. For ultrastructural investigations
fragments of kidney were prefixed in 2.7% glutaraldehyde solution and postfixed
in 2% osmic acid solution. The fragments were dehydrated in acetone and then
embedded in Vestopal W. The ultrathin sections were obtained using an LKB III
ultramicrotome and were contrasted with uranyl acetate. Examination of the sections
were performed in a TESLA-BS-500 electron microscope [1, 10, 13].
On the stained and contrasted sections we studied, by light and electron
microscopic examinations, the histological and ultrastructural modifications induced
by this anticancer drug in concordance with the moment of the sacrification.
Results and discussion. The light and electron microscopy investigations
of the kidney sections showed the appearance of some significant modifications
which seemed to be in concordance with the moment of the sacrification.
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