B. L. Van Duuren, A. Sivak, C. Katz
Sep 1, 1969
Citations
0
Influential Citations
25
Citations
Journal
British Journal of Cancer
Abstract
ACRIDINE orange, 3,6-bisdimethylamino-acridine (A.O.), exhibits a variety of effects in biological systems. Drosophila melanogaster (Clark, 1953); it also inhibits tumor induction on mouse skin in two-stage carcinogenesis (Van Duuren et al., 1969), and causes photo-dynamic inactivation of tobacco mosaic virus (Sastry and Gordon, 1966) and other viruses. Moreover, acridine orange has been shown to inhibit protein and nucleic acid biosynthesis in cell culture systems (Zelenin and Liapunova, 1964; Scholtissek and Becht, 1966). Because of these varied properties, the mode of interaction of the dye with nucleic acids, particularly DNA, has been widely studied by a variety of physical methods (Van Duuren, 1969) and several modes of binding of dye to nucleic acid have been proposed (Drummond et al., 1965). The relationship between the mode of action of carcinogens, mutagens and tumor-initiating agents is a problem of continuing interest (Trainin et al., 1964; Van Duuren and Sivak, 1968). Since little is known about the tumor-initiating and carcinogenic activity of acridine orange, it was of interest to examine these properties in mice and rats. The present report gives the results of these experiments. MATERIALS AND METHODS Animals. Mice were ICR/Ha Swiss obtained from Millerton Research Farms (Millerton, N.Y.). Females were used in all experiments. The mice were vaccinated against ectromelia at age 6 weeks and started on test at age 8 weeks. All mice were housed on sterilized wood chips in metal cages, 10 to a cage. Rats were female eastern Sprague-Dawley obtained from Blue Spruce Farms (Altamont, N.Y.). The rats were 6 weeks old and weighed 120-125 g. when testing began. They were housed in suspended wire mesh cages, 2 to a cage. Both mice and rats were fed Purina Laboratory Chow and water ad libitum. The animal rooms were temperature controlled at 22-24° C. Biological testing methods. Animals were weighed and observed monthly for the duration of the experiment. Tumors were recorded and counted at each observation. Any animal judged clinically to be in poor condition was sacrificed before the end of the experiment. All animals were examined carefully post-mortem and tumors and other lesions were excised for histological examination. Tissue sections were fixed in 10% formalin, blocked in paraffin and stained with hematoxylin and eosin. Routine sections of liver were also taken in the mouse skin treatment groups which received acridine orange repeatedly. The duration