The effects of N-dodecane pretreatment on the metabolism and distribution of benzo(A) pyrene in the isolated perfused rabbit lung

B(a)P is an ubiquitous potent carcinogen that has been associated with the increased incidence of human bronchiogenic carcinoma in occupational and urban populations. An isolated perfused rabbit lung preparation (IPL) was used to study the influence of pretreatment with a cocarcinogen, n-dodecane, on the metabolism of benzo (a)-pyrene (B(a)P). ¹⁴C-B(a)P was administered intratracheally to the IPL following biweekly inhalation exposure of the rabbits to n-dodecane. Results from n-dodecane pretreatment group were compared to those from the no-pretreatment group and an intratracheally administered B(a)P pretreatment group (B(a)P IT). Metabolites were isolated from serial blood samples up to 3 hours after administration of the ¹⁴C-B(a)P to the IPL. Patterns of B(a)P metabolites were determined using thin layer and high performance liquid chromatography, and liquid scintillation counting. The rates of appearance of B(a)P metabolites in the blood and the B(a)P metabolic pattern for n-dodecane groups were compared to B(a)P IT and no-pretreatment groups. The rates of appearance of metabolites in the blood (ng/hr/g of lung) were similar for B(a)P IT and n-dodecane pretreatment groups, but were five and four times greater, respectively, when compared to rates of appearance of metabolites for the no-pretreatment group. The B(a)P metabolic pattern of n-dodecane pretreatment showed an increase in the dihydrodiol and nonextractable formation and a decrease in the monohydroxy and diones compared to the no-pretreatment group. The metabolite pattern for B(a)P IT pretreatment group was similar to the metabolite pattern for the n-dodecane pretreatment group. The significance of the findings is that a known cocarcinogen, n-dodecane, appears to be as good an enzyme inducer as B(a)P in stimulating metabolism of B(a)P in lung. Therefore, man's risk in developing cancer may not be solely a result of exposure to a carcinogen, but may be dependent upon other constituents in his environment.