title: Higher incidence of lung adenocarcinomas induced by DMBA in connexin 43 heterozygous knockout mice.
abstract: Gap junctions are communicating junctions which are important for tissue homeostasis, and their disruption is involved in carcinogenic processes. This study aimed to verify the influence of deletion of one allele of the Connexin 43 gene on cancer incidence in different organs. The 7, 12-dimethylbenzanthracene (DMBA) carcinogenic model, using hebdomadary doses by gavage of 9 mg per animal, was used to induce tumors in Connexin 43 heterozygous or wild-type mice. The experiment began in the eighth week of the mice life, and all of them were euthanized when reaching inadequate physical condition, or at the end of 53 weeks. No statistical differences occurred for weight gain and cancer survival time (P = 0.9853) between heterozygous and wild-type mice. Cx43⁺/⁻ mice presented significantly higher susceptibility to lung cancer (P = 0.0200) which was not evidenced for benign neoplasms (P = 0.3449). In addition, incidence of ovarian neoplasms was 2.5-fold higher in Cx43⁺/⁻ mice, although not statistically significant. Other organs showed a very similar cancer occurrence between Cx43 groups. The experiment strengthens the evidence of the relationship between Connexin 43 deficiency and carcinogenesis.
authors.affiliation: Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Avenue Professor Dr. Orlando Marques de Paiva 87, 05508-900 Sao Paulo, SP, Brazil.
authors.forename: Krishna Duro
authors.initials: KD
authors.lastname: de Oliveira
authors.forename: Marcello Vannucci
authors.initials: MV
authors.lastname: Tedardi
authors.forename: Bruno
authors.initials: B
authors.lastname: Cogliati
authors.forename: Maria Lúcia Zaidan
authors.initials: ML
authors.lastname: Dagli
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000009:adverse effects / Q000494:pharmacology; D000230:Adenocarcinoma / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018031:Connexin 43; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D002273:Carcinogens; D018031:Connexin 43; C543076:GJA1 protein, mouse; D015127:9,10-Dimethyl-1,2-benzanthracene