Dose-response relationships for hepatic aflatoxin B1-DNA adduct formation in the rat in vivo and in vitro: the use of immunoslot blotting for adduct quantitation.
An immunoslot blotting (ISB) method for quantitating aflatoxin B1-DNA adduct levels has been developed and used to examine the relationship between dose and hepatic aflatoxin B1-DNA adduct levels in rats fed aflatoxin B1 (AFB1) in the diet at dose levels of between 0.5 and 10 micrograms/kg/day. The method has also been used to examine the dose-response relationship for adduct formation in precision-cut rat liver slices incubated with AFB1 at concentrations between 0.01 and 2 microM. For the feeding studies, groups of male Fisher F344 rats were given AFB1 in the diet for periods of 1 to 10 weeks and hepatic DNA adduct levels determined using ISB. The time for adduct levels to reach steady-state conditions was determined in animals given approximately 10 micrograms of AFB1/kg/day and steady-state levels at lower concentrations measured. The time course for the accumulation of AFB1-DNA adducts in rat liver slices incubated with AFB1 at 0.5 microM has been investigated and the relationship between adduct formation and AFB1 concentration over a wide concentration range in liver slices has been determined.
Phillips
J C
JC
BIBRA International, Carshalton, Surrey, United Kingdom.
Davies
S
S
Lake
B G
BG
D016604:Aflatoxin B1 / Q000494:pharmacology*; D000818:Animals; D018736:DNA Adducts / Q000096:biosynthesis*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D015151:Immunoblotting; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018736:DNA Adducts; D016604:Aflatoxin B1