Ž . Mutation Research 374 1997 209–231 Structural and mechanistic bases for the induction of mitotic ž / chromosomal loss and duplication ‘malsegregation’ in the yeast Saccharomyces cereÕisiae: Relevance to human carcinogenesis and developmental toxicology Mei Liu a , Stephen G. Grant a,b,c,d, ) , Orest T. Macina a,d , Gilles Klopman e , Herbert S. Rosenkranz a,d a Department of EnÕironmental and Occupational Health, UniÕersity of Pittsburgh, 260 Kappa DriÕe, Pittsburgh, PA 15238, USA b Department of Obstetrics, Gynecology and ReproductiÕe Sciences, UniÕersity of Pittsburgh, Pittsburgh, PA 15213, USA c Magee-Womens Research Institute, Pittsburgh, PA 15213, USA d UniÕersity of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA e Department of Chemistry, Case Western ReserÕe UniÕersity, CleÕeland, OH 44106, USA Received 24 September 1996; accepted 29 October 1996 Abstract MultiCASE has the ability to automatically determine the structural features responsible for the biological activity of chemicals. In the present study, 93 chemicals tested for their ability to induce chromosomal ‘malsegregation’ in the yeast Saccharomyces cereÕisiae were analyzed. This ‘malsegregation’ mimics molecular events that occur during human development and carcinogenesis resulting in an effective loss of one chromosome of an autosomal pair and duplication of the homologue. Structural features associated with the ability to induce such chromosome loss and duplication were identified and compared with those obtained from examination of other toxicological data bases. The most significant structural similarities were identified between the induction of chromosomal malsegregation and several toxicological phenomena such as cellular toxicity, induction of sister chromatid exchanges in vitro and rodent developmental toxicity. Very significant structural similarities were also found with systemic toxicity, induction of micronuclei in vivo and human developmental toxicity. Less significant structural overlaps were found between yeast malsegregation and rodent carcino- genicity, DNA reactivity and mutagenicity, and the induction of chromosome aberrations in vitro and sister chromatid exchanges in vivo. These overlaps may indicate mechanistic similarities between the induction of chromosomal malsegrega- tion and other toxicological phenomena. The predictivity of the SAR model derived from the present data base is relatively low, however. This may be merely a reflection of the small size and composition of the data base, however, further analyses suggest that it reflects primarily the multiple mechanisms responsible for the induction of chromosomal malsegregation in yeast and the complexity of the phenomenon. Keywords: SAR modeling; MultiCASE; Aneuploidy; Somatic mutation; Chromosome loss and duplication; Dosage compensation ) Ž . Ž . Corresponding author. Tel.: 412 967-6535; Fax: 412 624-1020; E-mail: sgg q@pitt.edu 0027-5107r97r$17.00 Copyright q 1997 Elsevier Science B.V. All rights reserved. Ž . PII S0027-5107 96 00236-9