A brief survey of the effects of potential antimetabolites and enzymes on the development of giant silkmoths

Abstract

More than 150 common purines, pyrimidines, purine and pyrimidine derivatives, and vitamin analogues were analysed for effects on insect growth and development. Compounds were injected into diapausing pupae of Samia cynthia and into pupae of Callosamia promethea just prior to the initiation of adult development. Most compounds were ineffective (e.g. uracil, 8-azaxanthine) or toxic (e.g. 6-methyl uracil, hypoxanthine). However, two classes of compounds had striking morphogenetic effects: the methyl xanthines (caffeine, theophylline, and theobromine) and barbituric acid and some of its analogues. The methyl xanthines prevented initiation of adult development but were not toxic to pupae, many of which lived more than 2 months after injection. These compounds specifically attacked the insect's central nervous system, causing extensive degenerative changes in the brain and segmental ganglia. They prevented adult development by damaging neurosecretory mechanisms within the brain. Barbituric acid and certain of its analogues (e.g. 5-amino uracil, 4,6-dihydroxy-pyrimidine, 1,3-dimethyl uracil, 6-methyl thiouracil) caused striking changes in the epidermis of developing adults but seemed to have little effect on the rest of the insect. The adults that emerged were almost devoid of scales, and the scales that did form were small and misshapen. Several proteases, esterases, and nucleases were also assayed for effects on development. Ribonuclease proved especially interesting, because in sublethal doses it caused abnormalities of the epidermis strikingly similar to those produced by barbituric acid. These results, and other evidence, suggest that both barbituric acid and ribonuclease interfere with the RNA metabolism of epidermal cells.