title: Lobular Distribution and Variability in Hepatic ATP Binding Cassette Protein B1 (ABCB1, P-gp): Ontogenetic Differences and Potential for Toxicity.
abstract: The ATP Binding Cassette B1 (ABCB1) transporter has critical roles in endo- and xenobiotic efficacy and toxicity. To understand population variability in hepatic transport we determined ABCB1 mRNA and protein levels in total liver lysates sampled from 8 pre-defined sites (n= 24, 18-69 years), and in S9 from randomly acquired samples (n= 87, 7 days-87 years). ABCB1 levels did not differ significantly throughout individual livers and showed 4.4-fold protein variation between subjects. Neither mRNA nor protein levels varied with sex, ethnicity, obesity or triglycerides in lysates or S9 (that showed the same relationships), but protein levels were lower in pediatric S9 (p< 0.0001), with 76% of adult ABCB1 present at birth and predicted to mature in 5 years. Pediatric total liver lysates were not available. In summary, opportunistic collection for studying human hepatic ABCB1 is acceptable. Additionally, ABCB1 may be lower in children, indicating differential potential for toxicity and response to therapy in this special population.
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawaii, Honolulu, HI 96813, USA. abandann@hawaii.edu.|Biotechnology Center, University of Yaoundé I, Yaoundé, Cameroon. abandann@hawaii.edu.
authors.forename: Ngu Njei
authors.initials: NN
authors.lastname: Abanda
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC V6T1Z3, Canada. zoe.riches@ubc.ca.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Riches
authors.affiliation: Department of Tropical Medicine, Medical Microbiology and Pharmacology, University of Hawaii, Honolulu, HI 96813, USA. abby.collier@ubc.ca.|Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC V6T1Z3, Canada. abby.collier@ubc.ca.
authors.forename: Abby C
authors.initials: AC
authors.lastname: Collier
keywords: development; elderly; obesity; pediatric; systemic toxicity