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The effects of avermectins on radiation-and dexamethasone-induced apoptosis of rat thymocytes have been studied. In particular, the properties of abamectin (avermectin B 1 ), ivermectin (22,23-dihydroavermectin B 1 , H 2 B 1 ) and aversectin C were examined. Aversectin C is a mixture of eight naturally occurring avermectins of the following composition: B 1 (42%), B 2 (22%), A 1 (13%) and A 2 (23%). This mixture is currently widely used as active ingredient in veterinary antiparasitic formulations produced by Pharmbiomed Co. Apoptosis was estimated by membrane damage, nuclear pycnosis (or chromatin condensation), DNA fragmentation and percentage of cells with subdiploid DNA. It was shown that aversectin C inhibits thymocyte apoptosis induced by both agents. The IC 50 dose was in the range of 0.1-0.3 µg/ml for aversectin C, whereas abamectin and ivermectin produced no effect up to 1 µg/ml. It is suggested that avermectins of the A series are responsible for the high anti-apoptotic activity exhibited by aversectin C. Thus, aversectin C is not only an effective antiparasitic drug but is also capable of exhibiting some other useful activities, e.g. a cytoprotective effect exerted on the mammalian immune cells. Avermectins, antiparasitic drugs, apoptosis, thymocytes, dexamethasone, gamma raysThe avermectins are a family of closely related 16-membered macrocyclic lactones produced by the fungus Streptomyces avermitilis. Nearly all the avermectins exhibit a broad spectrum of activity against nematode and arthropode parasites, with the B 1a compound being the most potent (Campbell 1989). Accordingly, it was used as active ingredient in commercial antiparasitic formulations. Until recently, there were basically two types of such avermectin-based active ingredients, i.e. ivermectin (consisting mainly of avermectin H 2 B 1a ) and abamectin (predominantly containing avermectin B 1a ). However, several years ago the Pharmbiomed Co. started manufacturing the veterinary and plant protection formulations based on a new active ingredient -aversectin C which is an intrinsic mixture of eight naturally occurring avermectins. Preliminary experiments demonstrated that aversectin C (presumably due to the presence of avermectins of both the A-and B-series) possesses some new useful features compared to ivermectin and abamectin, e.g. with the same high efficacy, the spectrum of activity is broader, level of residues is lower and, hence, the shorter withdrawal periods could be recommended (Simetsky et al. 1994;Berezkina et al. 1996). Furthermore, degradation of aversectin C in soil and water was found to be more effective compared to abamectin and ivermectin ( M o sin et al. 1998) and, hence, ecologically aversectin C is safer.

A natural avermectin complex, aversectin C, was shown to be capable of exerting selective cytostatic and neurotoxic effects on mammalian cells. Specifically, it killed proliferating neuroblastoma B103 cells but was non-toxic for differentiated cells of this culture. The antiproliferation action of aversectin C was not inhibited by bicuculline or picrotoxin, antagonists of the GABAalpha receptors, and was partly due to the action of avermectin A1, a component of aversectin C. Aversectin C irreversibly suppressed activity of 60% neurons in medial septal slices of the rat brain. More than 55% of them were the GABAalpha- and B1-sensitive neurons whereas the rest, about 45% neurons, were the GABAalpha-insensitive and the neurotoxic effect of aversectin C was caused mainly by the B2 component.

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The paradoxical reaction of Streptomyces avermitilis BKM Ac 1301 to ultraviolet light (UV) is revealed. The reaction manifests itself as a drop of lethal and mutagenic activities after exposure to increased dose of UV. Simultaneous changes in the survival of spores and in the number of morphological mutations associated with this reaction are proposed as a criterion for selecting effective doses of mutagen. Key Words: streptomycetes; mutagenesis; UV rays; criterionAvermectin-based preparations effectively control animal, plant, and human parasites. The nematocidal, acaricidal, and insecticidal activities of avermectins are due to blockade of synaptic transmission in invertebrates. The avermectin complex is produced by Streptomyces avermitilis [6]. Highly productive commercial strains are obtained by individual selection of strain and mutagen. We studied the specific reaction of Streptomyces avermitilis to ultraviolet (UV) exposure.It was expected that the regularities revealed would be helpful for the choice of effective doses and for the development of highly productive strains. with UV (dose range 1000-9000 erg/mm 2) by the conventional method [3]. Spores were kept at a low temperature for 7 days, seeded in Petri dishes with 2% glucose-potato agar, and incubated at 28~ in a thermostat. The lethal effect was assessed by counting the spores surviving after the exposure. Morphologically changed variants (MCV), biochemical mutants (auxotrophs), and changes in biosynthetic activity were assessed. Auxotrophs were detected by total sifting [2] on minimal medium with glucose. Biosynthetic activity (the capacity of a culture to produce avermectin) was assessed by accumulation of avermectins in the mycelium [4]. MATERIALS AND METHODS Streptomyces avermitilis RESULTSFigures 1 and 2 illustrate the relationships between the studied parameters of Streptomyces avermitilis culture (survival of spores, number of MCV, and activity of avermectin production) and UV dose. All these curves can be divided into two portions reflecting different patterns of changes; the critical