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Carcinogenic Effects of MGP-7 and B[a]P on the Hamster Cheek Pouch
1 The University of Texas M.D. Anderson Cancer Center, Department of Carcinogenesis, Smithville, TX 78957, USA Correspondence: Irma B. Gimenez-Conti, The University of Texas, M.D. Anderson Cancer Center, P.O. Box 389, 1808 Park Road 1-C, Smithville, TX 78957, USA; e-mail:igimenez{at}mdanderson.org. This study was performed to examine the carcinogenic effects of benzo[a]pyrene (B[a]P) and manufactured gas plant (MGP) residues on the hamster cheek pouch (HCP). Syrian hamsters were treated topically with a suspension of 2%, 10%, or 20% B[a]P or 50% or 100% MGP-7 (a mixture of residues from 7 MGP sites) in mineral oil for eight (short-term study) and sixteen, twenty, twenty-eight, and thirty-two weeks (long-term study). The short-term study showed that B[a]P induced p53 protein accumulation, indicative of genotoxic damage, as well as increased cell proliferation, hyperplasia, and inflammation, which is usually associated with promotional activity. In contrast, the MGP-7 presented only marginal p53 accumulation and induction of BrdU incorporation. In the long-term experiments, animals treated with 2% and 10% of B[a]P continued to show p53 protein accumulation as well as hyperplasia and increased cell proliferation and inflammation. By thirty weeks, all the animals treated with B[a]P had a 100% incidence of squamous cell carcinoma (SCC). Animals treated with 50% and 100% MGP-7 showed only weak hyperplasia and a low proliferation rate and accumulation of p53 protein through thirty-two weeks. Benzo[a]pyrene was highly carcinogenic when used at adequate doses. Manufactured gas plant residue, however, was not carcinogenic in this model.
Key Words: benzo[a]pyrene chemoprevention coal tar hamster cheek pouch manufactured gas plant residues oral cancer premalignant oral lesions Abbreviations: B[a]P, benzo[a]pyrene BrdU, 5-bromo-2-deoxyuridine DAB, 3, 3'-diaminobenzidine DMBA, dimethylbenz(a)anthracene H2O2, hydrogen peroxide HCP, hamster cheek pouch LI, labeling index MGP, manufactured gas plant residues PAH, polycyclic aromatic hydrocarbon SCC, squamous cell carcinoma
This version was published on October
1, 2009 Toxicologic Pathology, Vol. 37, No. 6,
733-740 (2009) |
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