Skin and lung carcinogenesis in mice Selected for acute inflammatory response (AIR). / Carcinogênese de pele e pulmão em linhagens de camundongos selecionados segundo a reatividade inflamatória aguda.

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

AIRmax mice are resistant and AIRmin susceptible to skin carcinogenesis by repeated DMBA doses. AIRmin mice developed initial contact hypersensitivity reaction (CHS) and late skin and lung tumors. The aryl hydrocarbon receptor (AHR) plays important roles in DMBA metabolism. Upon binding to agonist this transcription factor induces the expression of CYP P450 enzymes. Up regulated levels of IL1b, TNFa, IL6, TGFb1 and CYP1B1 mRNAs were found in the skin of AIRmin at 48h after DMBA. In AIRmax the levels were similar to controls. The cytokine and P450 mRNA up regulation in AIRmin is coherent with CHS elicitation by DMBA dependent on AHR activation. All AIRmax were found homozygous for the Ahrd allele, which confers resistance to CHS and carcinogenesis, whereas all AIRmin are homozygous for the Ahrb1 allele, related to susceptibility. The allelic segregation in the lines suggests that Ahr is a marker or a gene involved in carcinogenesis and in inflammatory response control. This last hypothesis was confirmed by linkage analysis of Ahr parental genotypes with acute inflammation degree in F2 (AIRmax x AIRmin) population. The results point to genetic and molecular factors underlying the differential susceptibility of AIRmax and AIRmin mice to carcinogenesis.

ASSUNTO(S)

aromatic hydrocarbon. hidrocarbonetos aromáticos. chemical carcinogens inflamação skin and lung neoplasia inflammation neoplasias cutâneas e de pulmão camundongos imunogenética mouse lines carcinógenos químicos immunogenetic

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