Effects of Intermittent Exposure to Aflatoxin B1 on DNA and RNA Adduct Formation in Rat Liver: Dose-Response and Temporal Patterns

Abstract

We studied the effects of intermittent exposure to aflatoxin B1 (AFB1) on hepatic DNA and RNA adduct formation. Fisher-344 male rats were fed 0.01, 0.04, 0.4, or 1.6 ppm of AFB1 intermittently for 8, 12, 16, and 20 weeks, alternating with 4 weeks of dosing and 4 weeks of rest. Other groups of rats were fed 1.6 ppm of AFB1 continuously for 4, 8, 12, and 16 weeks. Control rats received AFB1-free NIH-31 meal diet. AFB1-DNA and -RNA adducts were measured by HPLC with fluorescence detection. The data are presented as total DNA or RNA adducts. The DNA and RNA adduct levels increased or decreased depending on the cycles of dosing and rest. Rats removed from treatment 1 month after 1 or 2 dosing cycles (8 and 16 weeks of intermittent exposure) showed approximately a twofold decrease in DNA adduct levels and a two- to elevenfold decrease in RNA adduct levels compared with rats euthanized immediately after the last dosing cycle (12 and 20 weeks of intermittent exposure). Our data indicate that DNA and RNA adducts increased linearly, from 0.01 ppm to 1.6 ppm of AFB1 after 12 and 20 weeks of intermittent treatment. A linear dose response was also apparent for DNA but not for RNA adducts after 8 and 16 weeks of treatment. As biomarkers of exposure, AFB1-RNA adducts were three to nine times more sensitive than AFB1-DNA adducts but showed greater variability. These results suggest that binding of AFB1 to hepatic DNA is a linear function of the dose, regardless of the way this is administered. The dose-response relationship for RNA adducts depends on the length of the no-dosing cycles and on the turnover rate of RNA.

Antigenotoxic Effect of Piperine in Broiler Chickens Intoxicated with Aflatoxin B1

“…Some phytobiotics act as growth promoters and others can neutralize the toxic effects of xenobiotics like AFB 1 [43,49,50]. The covalent bonding of AFB 1 -epoxide with DNA modifies the structure of the nucleic acid and biological activity, generating RNA and DNA adducts with potential mutagenic, carcinogenic and teratogenic characteristics [51]. …”

Aflatoxin B1-induced hepatocellular carcinoma in developing countries: Geographical distribution, mechanism of action and prevention

“…Dietary exposure to carcinogens and mutagens depends on individual consumption patterns, which change with age, availability of food and lifestyle (64). Human and animal foods are commonly contaminated by aflatoxins during plantation, crop maturation, harvesting and storage.…”

Effect of curcumin on aflatoxin-induced biochemical changes in testis of mice

“…Sotomayor et al (7) suggested that binding of aflatoxin B 1 (AFB 1 ) to hepatic DNA in rat liver is a linear function of the dose, regardless of the way that it is administered. The doseresponse relationship for RNA adducts depends on the length of the no-dosing cycles and the turnover rate of RNA.…”