title: Sustained expression of CYPs and DNA adduct accumulation with continuous exposure to PCB126 and PCB153 through a new delivery method: Polymeric implants.
abstract: A new delivery method via polymeric implants was used for continuous exposure to PCBs. Female Sprague-Dawley rats received subcutaneous polymeric implants containing PCB126 (0.15% load), PCB153 (5% load), or both, for up to 45 days and release kinetics and tissue distribution were measured. PCB153 tissue levels on day 15 were readily detected in lung, liver, mammary and serum, with highest levels in the mammary tissue. PCB126 was detected only in liver and mammary tissues. However, a completely different pharmacokinetics was observed on co-exposure of PCB153 and PCB126, with a 1.8-fold higher levels of PCB153 in the liver whereas a 1.7-fold lower levels in the mammary tissue. PCB126 and PCB153 caused an increase in expression of key PCB-inducible enzymes, CYP 1A1/2 and 2B1/2, respectively. Serum and liver activities of the antioxidant enzymes, PON1 and PON3, and AhR transcription were also significantly increased by PCB126.32P-Postlabeling for polar and lipophilic DNA-adducts showed significant quantitative differences: PCB126 increased 8-oxodG, an oxidative DNA lesion, in liver and lung tissues. Adduct levels in the liver remained upregulated up to 45 days, while some lung DNA adducts declined. This is the first demonstration that continuous low-dose exposure to PCBs via implants can produce sustained tissue levels leading to the accumulation of DNA-adducts in target tissue and induction of indicator enzymes. Collectively, these data demonstrate that this exposure model is a promising tool for long-term exposure studies.
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202.|Department of Medicine, University of Louisville, Louisville, KY 40202.
authors.forename: Farrukh
authors.initials: F
authors.lastname: Aqil
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA 52242.
authors.forename: Hua
authors.initials: H
authors.lastname: Shen
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202.
authors.forename: Jeyaprakash
authors.initials: J
authors.lastname: Jeyabalan
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA 52242.
authors.forename: Xing
authors.initials: X
authors.lastname: Xin
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA 52242.|Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lehmler
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA 52242.|Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ludewig
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, IA 52242.|Department of Occupational and Environmental Health, University of Iowa, Iowa City, IA 52242.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Robertson
authors.affiliation: James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202.|Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202.
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Gupta
keywords: 32P-Postlabeling; CYPs; DNA adducts; PCB126 (3,3’,4,4’,5-pentachlorobiphenyl); PCB153 (2,2’4,4’,5,5’-hexachlorobiphenyl); Polymeric implants; paraoxonase 1 (PON1); polychlorinated biphenyls (PCBs)