title: Predicting chemically induced duodenal ulcer and adrenal necrosis with classification trees.
abstract: Binary tree-structured statistical classification algorithms and properties of 56 model alkyl nucleophiles were brought to bear on two problems of experimental pharmacology and toxicology. Each rat of a learning sample of 745 was administered one compound and autopsied to determine the presence of duodenal ulcer or adrenal hemorrhagic necrosis. The cited statistical classification schemes were then applied to these outcomes and 67 features of the compounds to ascertain those characteristics that are associated with biologic activity. For predicting duodenal ulceration, dipole moment, melting point, and solubility in octanol are particularly important, while for predicting adrenal necrosis, important features include the number of sulfhydryl groups and double bonds. These methods may constitute inexpensive but powerful ways to screen untested compounds for possible organ-specific toxicity. Mechanisms for the etiology and pathogenesis of the duodenal and adrenal lesions are suggested, as are additional avenues for drug design.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA.
authors.forename: C
authors.initials: C
authors.lastname: Giampaolo
authors.forename: A T
authors.initials: AT
authors.lastname: Gray
authors.forename: R A
authors.initials: RA
authors.lastname: Olshen
authors.forename: S
authors.initials: S
authors.lastname: Szabo
mesh_terms: D000307:Adrenal Gland Diseases / Q000139:chemically induced*; D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology*; D000465:Algorithms; D000478:Alkylation; D000818:Animals; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D004381:Duodenal Ulcer / Q000139:chemically induced*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced*; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations / Q000145:classification; D011336:Probability; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D004364:Pharmaceutical Preparations