Sustained release of benzo(a)pyrene from silicone polymer into the tracheobronchial tree of hamsters and dogs.
A method was developed to expose specific sites of the hamster and canine tracheobronchial tree to benzo(a)pyrene (BP) at quantitatively sustained rates. Implants for sustained release were formed by incorporating BP in a silicone rubber matrix at concentrations of 9.05 to 12%. Forty-nine hamsters and 12 dogs had a total of 86 implants surgically adhered to the tracheobronchial mucosa for up to 200 days. BP was released from the implants in hamsters and dogs as a first-order exponential function with a half-time of 54.8 and 44.5 days, respectively. Pathogenesis was progressively time and dose dependent. Squamous metaplasia with atypia regularly occurred in dogs within 150 days or after 7.17 mg BP and in hamsters after 50 days or 288 microgram BP. Bronchogenic cancers occurred in 93% of our hamsters after 100 days and 467 microgram BP. This method has applicability potentially as a bioassay for evaluating carcinogens in hamsters and currently as a means of producing a model of lung cancer in which neoplasia is induced at precise, selected sites.
D000818:Animals; D001580:Benzopyrenes / Q000008:administration & dosage* / Q000633:toxicity; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced; D006224:Cricetinae; D003692:Delayed-Action Preparations; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D005260:Female; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D008647:Mesocricetus; D008679:Metaplasia / Q000139:chemically induced; D011230:Precancerous Conditions / Q000139:chemically induced; D012828:Silicones; D014132:Trachea / Q000187:drug effects* / Q000473:pathology
D001580:Benzopyrenes; D002273:Carcinogens; D003692:Delayed-Action Preparations; D004343:Drug Implants; D012828:Silicones