Organ-specific distribution of genotoxic effects in mice exposed to cooked food mutagens

Abstract

The induction of organ-specific genotoxic effects of five cooked food mutagens in Swiss albino mice was investigated in microbial animal-mediated assays. The indicator of the induction of DNA damage was a pair of Escherichia coli K12 strains, differing vastly in repair capacity (uvrB/recA versus uvr+/rec+). All compounds gave positive results in the tested dose range between 2.5 and 40 mg/kg body weight (i.p. administration, exposure time 120 min). 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) were slightly more genotoxic than 2-amino-3,8-dimethylimidazo[4,5-f]quinoline (MeIQx), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) which caused similar effects. When the compounds were administered orally, higher doses were required to induce repairable DNA damage. The pattern of organ-specific effects was essentially similar for all compounds; genotoxicity was most pronounced in livers and lungs, whereas in kidneys, spleen and testes comparatively lower effects were measured. The activity of PhIP, MeIQ and IQ in the blood was similar to that observed in the liver. The results obtained in vivo were compared with data gained in vitro with subcellular organ fractions. Our findings indicate the following. (i) The concentrations required to induce repairable DNA damage in microbial animal-mediated assays are substantially higher than might be expected on the basis of the liquid suspension tests. (ii) The ranking order of the genotoxicity of the various compounds in vitro is similar to that measured in vivo, but the differences in genotoxic potencies are less pronounced in the living animal.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA adducts of heterocyclic amine food mutagens: implications for mutagenesis and carcinogenesis

“…In contrast, AIAs have been shown to induce base substitution and/or deletion mutations in vivo in the lacI or lacZ mutational reporter gene of transgenic mice (187)(188)(189)(190)(191)(192)(193), the colonic crypt cells of mice (194)(195)(196), Dlb-1-specific locus test in mouse small intestine (191,197,198) and the animal-mediated microbial assay system (199).…”

Specific Desmutagens (Antimutagens) in Oregano against a Dietary Carcinogen, Trp-P-2, Are Galangin and Quercetin

“…Of the 10 pyrolysates identified as the carcinogens, 3-amino-l-methyl-5iT-pyrido[4,3-6]indole (Trp-P-2) is a liver-specific carcinogen (Wakabayashi et al, 1992;Knasmüller et al, 1992), is one of the strongest mutagens (Sugimura, 1985), and occurs frequently in our diet (Yamaizumi et al, 1980). It is very important to mitigate the cancer risk from Trp-P-2 in our daily life, and therefore we have an interest in dietary compounds which can neutralize Trp-P-2.…”

Spermatogenesis Is Not Impaired in a Nucleotide Excision Repair-Deficient Min Mouse Model With or Without Neonatal Mutagen Treatment

“…Consequently, 5 mg/kg PhIP is considered a genotoxic dose. It has been shown in earlier studies that PhIP induces bulky DNA adducts in testicular tissue of adult mice and rats at 2.5 to 40 mg/kg bw and 50 mg/kg bw, respectively (Knasmuller et al, 1992; Huber et al, 1997). Similarly, in vivo exposure to other environmental agents such as B(a)P has been shown to give rise to DNA adducts in adult male testicular cells residing within the testis barrier (Olsen et al, 2010; Verhofstad et al, 2010).…”

“…This shows that PhIP was metabolized and reached target organs (Steffensen et al, 2006). Knasmuller et al (1992) reported that PhIP treatment of adult mice induced PhIP–DNA adducts in testicular cells. Our hypothesis is that PhIP treatment leads to the formation of bulky DNA adducts, which, if they remain unrepaired, may interfere with DNA replication and cell division.…”