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Toxicologic Pathology
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Articles

Carcinogenic Effects of MGP-7 and B[a]P on the Hamster Cheek Pouch

Jimi Lynn Brandon1, Claudio J. Conti1, Lawrence S. Goldstein2, John DiGiovanni1 and Irma B. Gimenez-Conti1

1 The University of Texas M.D. Anderson Cancer Center, Department of Carcinogenesis, Smithville, TX 78957, USA
2 Electric Power Research Institute, Palo Alto, CA 94303, 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)
DOI: 10.1177/0192623309344203


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