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Ultrastructural Alterations Produced by Polycyclic Aromatic Hydrocarbons on Rat Tracheal Epithelium in Organ Culture¹

Cancer Research Institute and Department of Medicine, School of Medicine, University of California San Francisco Medical Center, San Francisco, California 94122

Ultrastructural alterations of columnar respiratory epithelium were produced by certain polycyclic aromatic hydrocarbons in suckling rat trachea maintained in organ culture for 11 days. The potent carcinogens 7,12-dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene and the weakly carcinogenic compounds benz(a)anthracene and 5-fluoro-7,12-dimethylbenz(a)anthracene (F-DMBA) produced cells whose cytoplasm contained little endoplasmic reticulum, many free ribosomes, complex autophagic vacuoles, and abundant cytoplasmic filaments. These cells were often connected by many desmosomes and complex interdigitations in a stratified epithelium 3 to 8 cells high, which bore a similarity to stratified squamous epithelia such as skin and also resembled bronchogenic carcinoma in situ. Some nucleolar fragmentation and disorganization also occurred in the epithelium of the carcinogentreated explants. In general, DMBA produced morphologic abnormalities at low concentrations, while the related compounds benz(a)anthracene and F-DMBA did so at concentrations 12.5- to 25-fold higher. Although autophagic vacuoles and related structures, as well as some degree of disorganization of the endoplasmic reticulum, were found in columnar cells, and increased filaments were noted in basal cells, extensive alteration of cell structure and epithelial state was not encountered in control explants or in explants treated with anthracene, benzo(e)pyrene, benzo(a)fluorene, benz(m,n,o)fluoranthene, chrysene, perinaphthoxanthene, perylene, or phenanthrene.

¹ Supported in part by Research Contract PH 43-64-42, National Cancer Institute, USPHS, and by cancer research funds of the University of California.

Received 8/14/67. Accepted 1/12/68.

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