This Article Free Full Text (Free PDF) Free References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Bolon, B. Articles by Morgan, K. T. Search for Related Content PubMed PubMed Citation Articles by Bolon, B. Articles by Morgan, K. T. Social Bookmarking                         What's this?

Histopathologic Approaches to Chemical Toxicity Using Primary Cultures of Dissociated Neural Cells Grown in Chamber Slides

Chemical Industry Institute of Toxicology, 6 Davis Drive, P.O. Box 12137, Research Triangle Park, North Carolina 27709, Pathology Associates, Inc., 15 Worman's Mill Ct., Suite 1, Frederick, Maryland 21701.

David C. Dorman

Chemical Industry Institute of Toxicology, 6 Davis Drive, P.O. Box 12137, Research Triangle Park, North Carolina 27709

Marc S. Bonnefoi

Chemical Industry Institute of Toxicology, 6 Davis Drive, P.O. Box 12137, Research Triangle Park, North Carolina 27709, Rhône-Poulenc Rorer Central Research, Collegeville, Pennsylvania 19426

Holly W. Randall

Chemical Industry Institute of Toxicology, 6 Davis Drive, P.O. Box 12137, Research Triangle Park, North Carolina 27709, SRI International, Life Sciences Division ST1-2, 333 Ravenswood Ave., Menlo Park, California 94025

Kevin T. Morgan

Chemical Industry Institute of Toxicology, 6 Davis Drive, P.O. Box 12137, Research Triangle Park, North Carolina 27709

Morphologic lesions have received only limited attention as in vitro endpoints of toxicity. In the present work, "tissue" and cell morphology of control and toxicant-treated primary dissociated cerebrocortical cell cultures from fetal mice were examined using phase-contrast and bright-field microscopy. In untreated control cultures, a reproducible sequence of developmental events included cellular reaggregation, intercolony bridging with cell migration, and neuronal apoptosis, with maturation yielding confluent monolayers containing both neurons and glia. Because even mature cultures had regions of varying differentiation, an understanding of the normal developmental sequence was essential when assessing toxicant-treated cultures for damage. Chemicals induced neuronotoxic, gliotoxic, and cytotoxic (i.e., nonspecific) patterns of morphologic damage in growing (<6 day old) or mature (6-15 day old) cultures in both a concentration-dependent and cell type-specific manner. In addition, exposure to some toxicants consistently reduced the staining intensity for glial fibrillary acidic protein in the astrocyte carpet prior to the appearance of structural damage. These data indicate that histopathologic endpoints, including methods for neural-specific markers, represent potentially valuable criteria for in vitro assessments of neurotoxicity.

Key Words: Neurotoxicity • neuropathology • in vitro • apoptosis • enzyme cytochemistry • immunocytochemistry

Toxicologic Pathology, Vol. 21, No. 5, 465-479 (1993)
DOI: 10.1177/019262339302100506


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				K. T. Morgan, M. Pino, L. M. Crosby, Min Wang, T. C. Elston, Z. Jayyosi, M. Bonnefoi, and G. Boorman Complementary Roles for Toxicologic Pathology and Mathematics in Toxicogenomics, With Special Reference to Data Interpretation and Oscillatory Dynamics Toxicol Pathol, January 1, 2004; 32(1_suppl): 13 - 25. [Abstract] [PDF]

				K. T. Morgan, Hong Ni, H. R. Brown, L. Yoon, C. W. Qualls JR, L. M. Crosby, R. Reynolds, B. Gaskill, S. P. Anderson, T. B. Kepler, et al. Application of cDNA Microarray Technology to In Vitro Toxicology and the Selection of Genes for a Real-Time RT-PCR-Based Screen for Oxidative Stress in Hep-G2 Cells Toxicol Pathol, June 1, 2002; 30(4): 435 - 451. [Abstract] [PDF]

				U. Namgung and Z. Xia Arsenite-Induced Apoptosis in Cortical Neurons Is Mediated by c-Jun N-Terminal Protein Kinase 3 and p38 Mitogen-Activated Protein Kinase J. Neurosci., September 1, 2000; 20(17): 6442 - 6451. [Abstract] [Full Text] [PDF]

				B. Bolon Comparative and Correlative Neuroanatomy for the Toxicologic Pathologist Toxicol Pathol, January 1, 2000; 28(1): 6 - 27. [Abstract] [PDF]