© 1995 Oxford University Press
research-article |
Kinetics of Hemoglobin and Albumin Adducts in Rabbits Subchronically Exposed to Benzo[a]pyrene1
Département de médecine du travail el d'hygiène du milieu. University of Montreal, P O Box 6128, Stn A, Montreal, Quebec H3C 3J7, Canada
Received September 13, 1993; accepted July 11, 1994
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 µmol·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 µmol 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 µmol 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. Comparison of the pattern of hemoglobin adduct formation and removal with currently proposed kinetic adduct model could only be performed for the 5 µmol BaP·kg–1·week–1 dose as hemoglobin adduct concentrations fell below detection limit after cessation of exposure at the lower dose. The higher dose data suggested that the model reasonably describe the overall profile observed. However, this limited comparison also suggested that, for hydrophobic substances such as BaP capable of enzymatic induction, introduction of both an induction function and consideration of the kinetics of the parent compound itself in the organism would probably improve the fit.