title: Differences in the tumorigenic activity of a pure hydrocarbon and a complex mixture following ingestion: benzo[a]pyrene vs manufactured gas plant residue.
abstract: The tumorigenic activity of manufactured gas plant residue (MGP) was evaluated in female A/J mice using a F0927 basal gel diet system. Adulterated diets containing MGP (0.10% or 0.25%) or benzo[a]pyrene (B[alpha]P; 16 or 98 ppm) were fed for 260 days. A negative control group was maintained on a nonadulterated basal gel diet. Mice dosed with a single ip injection of 1.79 mg of B[a]P in a tricaprylin vehicle and maintained on a NIH-07 pellet diet were positive controls. In addition, a nontreated group of mice and a group dosed with vehicle only were maintained on a NIH-07 pellet diet and used as negative controls. Animal body weight and consumption of MGP and B[a]P were monitored throughout the study. Ingestion of a 0.10 or 0.25% MGP adulterated diet resulted in 70 and 100% of the mice developing lung tumors with a multiplicity of 1.19 and 12.17 tumors/mouse, respectively. Mice maintained on a 0.10% MGP diet consumed 0.7 g of MGP containing 1.8 mg of B[a]P while those fed a 0.25% MGP diet ingested 1.5 g of MGP containing 4.2 mg of B[a]P. The incidence of lung tumors in mice fed only B[a]P was considerably lower than that observed for animals fed a MGP diet. A diet containing 98 ppm B[a]P produced a significant incidence of tumor-bearing mice with 52% developing lung tumors. The multiplicity observed in these animals, however, was not significant at 0.59 tumors/mouse. A diet containing 16 ppm B[a]P did not produce a significant tumorigenic response in lung. Animals fed a 16 or 98 ppm B[a]P diet consumed a total of 11 and 67 mg of B[a]P, respectively. A single ip dose of B[alpha]P (1.79 mg in 0.25 mL of tricaprylin) resulted in 100% lung tumorigenesis with a multiplicity of 15.79 tumors/mouse. In contrast to observed induction of lung tumors, no forestomach tumors were detected in any animal fed a 0.10 or 0.25% MGP adulterated diet. However, ingestion of a diet containing only 16 or 98 ppm of B[a]P resulted in 20 and 100% of the mice developing forestomach tumors, respectively. The multiplicity for forestomach tumors was 0.24 and 4.22 tumors/mouse, respectively. The incidence of forestomach carcinomas in tumor bearing mice was 8 and 52%, respectively. The ip administration of 1.79 mg of B[a]P resulted in an 83% forestomach tumor incidence having a multiplicity of 1.83 tumors/mouse. Forestomach carcinomas were induced in 34% of the mice exhibiting forestomach tumors. These data indicate that chronic ingestion of MGP- or B[a]P-adulterated diets produces significant differences in the tumorigenic response of female A/J mouse forestomach and lung tissues.
authors.affiliation: Department of Pharmaceutical Chemistry, Rutgers, State University of New Jersey, College of Pharmacy, Piscataway 08855-0789, USA.
authors.forename: E H
authors.initials: EH
authors.lastname: Weyand
authors.forename: Y C
authors.initials: YC
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: A
authors.initials: A
authors.lastname: Koganti
authors.forename: H A
authors.initials: HA
authors.lastname: Dunsford
authors.forename: L V
authors.initials: LV
authors.lastname: Rodriguez
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D003033:Coal Tar / Q000633:toxicity*; D004032:Diet; D005260:Female; D007220:Industrial Waste / Q000009:adverse effects*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000473:pathology; D015430:Weight Gain / Q000187:drug effects
chemical_list: D002273:Carcinogens; D007220:Industrial Waste; D011084:Polycyclic Aromatic Hydrocarbons; D001564:Benzo(a)pyrene; D003033:Coal Tar