title: Pilot studies evaluating the lung tumor yield in cigarette smoke-exposed mice.
abstract: In spite of the major role played by cigarette smoking in the epidemiology of lung cancer, it is very difficult to reproduce the carcinogenicity of this complex mixture in animal models. We implemented a series of pilot experiments in three mouse strains, exposed either to environmental cigarette smoke (ECS) or mainstream cigarette smoke (MCS) or its condensate (MCSC). The whole-body exposure of Aroclor-treated A/J mice to ECS resulted in a rapid and potent induction of micronuclei in peripheral blood erythrocytes. After 6 months of exposure, 6 h a day, followed by 4 months of recovery in filtered air, both lung tumor incidence and multiplicity were significantly increased as compared to sham-exposed mice (77.8% vs. 22.2%, and 1.11+/-0.26 vs. 0.22+/-0.15, means +/- SE). Multiple i.p. injections of butylated hydroxytoluene did not significantly enhance the tumor yield. Another experiment confirmed the responsiveness of A/J mice exposed to ECS for 5 months, followed by 4 months of recovery in air (75.0% vs. 25.0%, and 1.05+/-0.17 vs. 0.25+/-0.10). In contrast, the increase in lung tumor yield after exposure to ECS for 2 months, followed by recovery in air for 7 months, was not significant, and the continuous exposure to ECS for 9 months was totally ineffective. These data, in agreement with previous results of others, show that exposure of A/J mice to ECS for 5-6 months, followed by recovery in air for 4 months, is successful in inducing a weak but significant and reproducible increase in lung tumor yield. Furthermore, the simultaneous exposure to the light emitted by halogen quartz bulbs for 9 months and to ECS for 5 months, followed by 4 months in air, was again weakly tumorigenic (incidence of 55.0% and multiplicity of 0.75+/-0.19), whereas exposure to both ECS and light for 9 months was devoid of effect. The whole-body exposure of A/J mice to MCS, 1 h a day for 5 months, or weekly i.p. injections of MCSC for 5 months, followed in both cases by 4 months of recovery in air, failed to enhance the lung tumor yield. The whole-body exposure of SKH-1 hairless mice to ECS for 6 months, followed by exposure to halogen light for 8 months, resulted in the formation of multiple skin tumors but failed to produce lung tumors. The whole-body exposure of C57BL/6 mice to ECS for 6 months failed to induce any lung tumor but caused alopecia, gray hair, and hair bulb cell apoptosis, which were prevented by the oral administration of N-acetylcysteine.
authors.affiliation: Department of Health Sciences, Section of Hygiene and Preventive Medicine, University of Genoa, Genoa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: D'Agostini
authors.forename: R M
authors.initials: RM
authors.lastname: Balansky
authors.forename: C
authors.initials: C
authors.lastname: Bennicelli
authors.forename: R A
authors.initials: RA
authors.lastname: Lubet
authors.forename: G J
authors.initials: GJ
authors.lastname: Kelloff
authors.forename: S
authors.initials: S
authors.lastname: De Flora
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000236:Adenoma / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001835:Body Weight; D002084:Butylated Hydroxytoluene / Q000633:toxicity; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity; D020732:Cytogenetic Analysis; D004249:DNA Damage / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects; D005260:Female; D015994:Incidence; D007274:Injections, Intraperitoneal; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008812:Mice, Hairless; D008810:Mice, Inbred C57BL; D010865:Pilot Projects; D012907:Smoking / Q000009:adverse effects*
chemical_list: D004273:DNA, Neoplasm; D020111:Chlorodiphenyl (54% Chlorine); D002084:Butylated Hydroxytoluene; D000111:Acetylcysteine