Adriamycin isolated from Streptomyces peucetius var caesius, is of very potent cytotoxic to mammalian cells both in vitro and in vivo. So it has been widely used in clinics for treatment of many solid tumors.
It is well known that adriamycin inhibits DNA and RNA synthesis in mammalian cells. Possible mechanisms accounting for the inhibitory effect of adriamycin include 1) interference of the template activities of the DNA by incorporating with DNA double helix; and 2) inhibition of the action of the DNA dependent DNA polymerase.
Unfortunately, adriamycin offers little, if any, specificity and it is equally active against tumors and normal cells.
The author has demonstrated the effect of adriamycin on the parietal cells of hamster, histologically observing the morphological changes of the cells by the use of light and electron microscopes. The animals treated with 50mg per kg of adriamycin were sacrificed at 12 and 24 hours after the drug administration. The animals of the control group were administered only water for injection. All animals were starved for 12 hours before sacrificing them. The parts of stomach specimens fixed in 10% neutral formalin and prepared by way of hematoxylin and eosin and the other parts of specimens, which prefixed in 2% glutaraldehyde-2.5% paraformaldehyde phosphate buffer and post-fixed in the 1% oxmic acid, were dehydrated and embedded in the
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Epon 812. Ultrathin sections, 600-800 A thickness, were made and double stained with uranyl acetate and lead citrate. And these preparations were observed with light and JEM 100cx-II electron microscopes.
The results were as follows.
1. The dilatation of the lumens due to severely atrophied living cells of gastric glands were seen. Vacuolar degeneration and pyknosis happened to atrophied parietal cells. In the fundus of gastric gland, many parietal cells and mucous neck cells were also found at 24 hours after drug administration.
2. The membrane bound ribosomes of the cisternae of the rough endoplasmic reticulum were detached. Irregularly shaped mitochondria, many lipid droplets and numerous autophagic vacuoles were observed. `C´ shaped and concentric structured components of the tubulovesicle were also found in the parietal cells. Consequently, it is suggested that adriamycin would induce the damage of the
organelles of parietal cells in hamsters.
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