A novel aromatic mutagen, 5-amino-6-hydroxy-8H-benzo[6,7]azepino[5,4,3-de]quinolin-7-one (ABAQ), induces colonic preneoplastic lesions in mice

Abstract

The benzoazepinoqunolinone derivative, 5-amino-6-hydroxy-8H-benzo[6,7]azepino[5,4,3-de]quinolin-7-one (ABAQ), which is produced in a mixture of glucose and tryptophan incubated at 37 °C under physiological conditions in the presence or absence of hydroxyl radicals caused by the Fenton reaction, is a novel aromatic mutagen. In the current study, we determined the tumor-initiating potency of ABAQ using an inflammation-relate, two-stage mouse colon carcinogenesis model. Male Crj: CD-1 (ICR) mice were treated with the single intragastric administration (100 or 200 mg/kg body weight) of ABAQ followed by subsequent 1-week oral exposure to 2% dextran sodium sulfate (DSS) in drinking water. The ABAQ treatment alone resulted in high-grade dysplasia, which is a precursor to colorectal cancer, in the colon. Following the administration of DSS after ABAQ treatment, the incidence and frequency of high-grade dysplastic lesions increased; the values were highest in the mice treated with 200 mg/kg body weight of ABAQ followed by DSS. The lesions expressing β-catenin in their nuclei and cytoplasm exhibited high proliferation activity without the expression of programmed cell death 4. These findings indicate that ABAQ has a tumor-initiating activity in the mouse colon, with or without inflammation, although the potential pro-inflammatory effect of high doses of ABAC should be investigated.

Keywords

• Benzoazepinoqunolinone
• Heterocyclic amines
• Maillard reaction
• Fenton reaction
• High-grade dysplasia
• PDCD4
• Colon
• Dextran sodium sulfate
• Initiation
• Mice