The transport and localization of benzo(a)pyrene-hematite and hematite-210Po in the hamster lung following intratracheal instillation.

When administered intratracheally adsorbed onto hematite carrier particles, 210Po and benzo( a )pyrene (BP) induce lung tumors of different histologies and apparent sites of origin. Hematite-210Po produces combined epidermoid and adenocarcinomas in the peripheral lung, while BP-hematite produces mainly epidermoid carcinomas of the major bronchi and trachea. To determine whether cells in the lung are differentially sensitive to the two types of carcinogen or whether the carcinogens are reaching and acting at different sites, we have studied their transport and localization following intratracheal administration on carrier particles: 210Po localization by freeze-dry autoradiography and BP by ultraviolet light fluorescence microscopy of frozen sections. The results show that 210Po represents a firmly bound insoluble carcinogen which delivers its primary dose to the peripheral lung from the particles that are retained in the alveolar duct region. BP, on the other hand, is a loosely bound soluble carcinogen which leaves the carrier particles and enters upper airway epithelial cells during clearance of the particles on the mucous ciliary escalator. We thus conclude that BP induces central tumors because a significant amount of the carcinogen reaches the upper airway epithelial cells, while 210Po induces peripheral tumors because the major radiation dose is delivered to the alveolar region.