Genotoxicity, carcinogenicity, and mode of action of the fried food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ).

Abstract

Because mutagens typified by 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) observed in cooked foods are widely consumed, detailed studies of their biochemical and biological properties including carcinogenicity are most important. IQ induces unscheduled DNA synthesis in liver cells, which when taken together with its powerful mutagenicity in the Salmonella typhimurium test system, predicts carcinogenicity. In female Sprague-Dawley rats, IQ did exhibit potent carcinogenicity for the mammary gland, the ear duct, and to a lesser extent, pancreas and bladder. Data from Japanese laboratories indicate carcinogenicity also to the intestinal tract. Thus, one of the mutagens formed during cooking is a versatile carcinogen that because of extensive human intake requires urgent exploration for specific human cancer risk.

β-Glucuronidases of opportunistic bacteria are the major contributors to xenobiotic-induced toxicity in the gut

“…Indeed, gut bacterial GUSs are involved in the toxicity of carcinogenic aromatic compounds. For example, the carcinogenicity of hetero-aromatic compounds that is produced during meat processing was found to be associated with gut bacterial uid A (also known as gus A) 18 . In addition, bacterial GUS activity in the cecum delays elimination of the endocrine-disrupting agent, bisphenol A 19 .…”

The Effect of Flavonoids in Soybean Products in Lymphocytes from IBD and Colon Cancer Patients After Treatment with Food Mutagens and Hydrogen Peroxide

“…The genotoxicity of HCA originates from their activation by a series of reactions involving cytochrome P450 when the parent compound is converted to an electrophilic derivative such as a nitrenium ion that covalently binds to DNA resulting in DNA adducts and subsequently in nucleotide alterations and chromosomal aberrations (Goldman and Shields, 2003;Hatch et al, 2001). IQ induces unscheduled DNA synthesis in liver cells and shows strong mutagenic properties in the Salmonella typhimurium test system, which contribute to its classification as a potent carcinogen (Maeda et al, 1999;Murata et al, 1999;Weisburger et al, 1986) Also in addition to the formation of DNA adducts, oxidative damage to the DNA itself plays a crucial role in the carcinogenic process of food mutagens (Maeda et al, 1999;Murata et al, 1999). Heterocyclic amines like IQ are able to generate free radicals in the presence of NADPH and cytochrome b5 reductase (Maeda et al, 1999).…”