Kinetics of hemoglobin and albumin adducts in rabbits subchronically exposed to benzo[a]pyrene.

Benzo[a]pyrene (BaP) can form adducts with proteins after activation to a diolepoxide. Benzo[a]pyrene-hemoglobin and BaP-albumin adducts were measured in rabbits exposed to 0.5 or 5 mumol.kg-1.week-1 for a total of 11 weeks (last injection on Day 75). Each dose group of nine rabbits was divided into three equal subgroups. For each dose, one subgroup received a single weekly injection (Mondays), the second had two equal weekly injections (Mondays and Thursdays), and the third had five weekly injections (Mondays through Fridays). Blood was collected prior to injection on Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 77, 78, 80, 84, 92, 108, and 140 for adducts determinations, with Day 0 being a Monday. The measured concentration of hemoglobin adducts was independent of the frequency of administration for a given total weekly dose giving support to its value as a "biointegrator." In addition, animals injected with 0.5 and 5 mumol BaP.kg-1.week-1 had respective mean adduct concentrations of 0.3 and 3 pmol/g hemoglobin. The blood concentration of albumin adducts was related to the frequency of injection with the animals receiving one, two and five injections/week having the lowest, intermediate, and highest adduct concentrations, respectively. Animals injected with 0.5 and 5 mumol BaP.kg-1.week-1 had respective mean adduct concentrations of 5 and 20 pmol/g which are 17 and 7 times higher than their corresponding hemoglobin adducts' values. The corresponding albumin adducts' half-lives calculated from the day of cessation of exposure were 5.8 and 9.6 days, compared with a reported 5.7 days for the half-life of the intact protein.(ABSTRACT TRUNCATED AT 250 WORDS)