title: Measurement of chemically induced cell proliferation in rodent liver and kidney: a comparison of 5-bromo-2'-deoxyuridine and [3H]thymidine administered by injection or osmotic pump.
abstract: Different labeling methods for quantitating cell proliferation were evaluated in livers and kidneys of control and chemically treated mice and rats. The percentage of cells in S-phase (labeling indices) were compared in tissues of animals given either 5-bromo-2'-deoxyuridine (BRDU) or [3H]thymidine. These DNA precursor labels were delivered either by a single i.p. injection 2 h prior to killing the animals or via the s.c. implanted osmotic pump for 3 or 6 days. B6C3F1 mice and male F344 rats were exposed to either a peroxisome proliferator and hepatocarcinogen, Wy-14,643 (WY), in the diet at 0.1% for up to 5 days, or a non-genotoxic mouse liver and male rat kidney carcinogen, 1,4-dichlorobenzene (DCB), in corn oil by gavage for up to 5 days in mice (600 mg/kg/day) or up to 3 weeks in rats (300 mg/kg/day, 5 days per week). Labeling indices (LIs) in the liver and kidney were similar in BRDU- and [3H]thymidine-labeled mice and rats. Cell proliferation was increased in livers of both species of WY- and DCB-treated animals when compared to controls. After 4 days of chemical treatment with continuous administration of a DNA precursor label during the last 3 days of treatment, LIs in controls, DCB- and WY-treated mouse livers were 0.7, 19 and 17% for BRDU and 0.9, 15 and 13% for [3H]-thymidine respectively. Furthermore, BRDU and [3H]-thymidine labeled the same population of cells as revealed by similar patterns of cell labeling in the livers and kidneys of treated animals. The LI for BRDU- and [3H]thymidine-labeled renal proximal tubular cells was 7.7 and 8.0% respectively, in rats receiving DCB for 4 days and DNA precursor label during the last 3 days of treatment, while the LI for controls was 4.3 and 3.7% respectively. The renal proximal tubular cell LI increased to 11% in BRDU-labeled rats treated with DCB for 3 weeks. LIs in both liver and kidney were greatest in control and treated animals that received the DNA precursor label via osmotic pumps for 6 days, and least in 2 h pulse-labeled animals. However, induction of hepatic LI in treated over control animals was greatest for treated animals labeled for 3 days. These results demonstrate comparable cell labeling of cells in S-phase with either BRDU and [3H]thymidine labeling methods. BRDU presents no radioactive containment problems, and results are obtained more rapidly than [3H]thymidine.(ABSTRACT TRUNCATED AT 400 WORDS)
authors: Chemical Industry Institute of Toxicology, Research Triangle Park, NC 27709.
authors: S R
authors: SR
authors: Eldridge
authors: L F
authors: LF
authors: Tilbury
authors: T L
authors: TL
authors: Goldsworthy
authors: B E
authors: BE
authors: Butterworth
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002722:Chlorobenzenes / Q000494:pharmacology; D007263:Infusions, Parenteral; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D016196:S Phase / Q000187:drug effects; D013936:Thymidine / Q000494:pharmacology*
chemical_list: D002273:Carcinogens; D002722:Chlorobenzenes; D011743:Pyrimidines; C006253:pirinixic acid; C018511:4-dichlorobenzene; D007064:L-Iditol 2-Dehydrogenase; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001973:Bromodeoxyuridine; D013936:Thymidine