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.
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http://dx.doi.org/10.1177/0192623309344203 | DOI Listing |
Nucleic Acids Res
January 2025
Ophthalmology, University of North Carolina, 130 Mason Farm Rd, Chapel Hill, NC 27517, USA.
Adeno-associated virus (AAV) inverted terminal repeats (ITRs) induce p53-dependent apoptosis in human embryonic stem cells (hESCs). To interrogate this phenomenon, a synthetic ITR (SynITR), harboring substitutions in putative p53 binding sites was generated and evaluated for vector production and gene delivery. Replication of SynITR flanked transgenic genome was similar compared to wild type (wt) ITR, with a modest increase in vector titers.
View Article and Find Full Text PDFIntegration of DNA replication with DNA repair, cell cycle progression, and other biological processes is crucial for preserving genome stability and fundamentally important for all life. Ataxia-telangiectasia mutated and RAD3-related (ATR) and its partner ATR-interacting protein (ATRIP) function as a critical proximal sensor and transducer of the DNA Damage Response (DDR). Several ATR substrates, including p53 and CHK1, are crucial for coordination of cell cycle phase transitions, transcription, and DNA repair when cells sustain DNA damage.
View Article and Find Full Text PDFAME Case Rep
December 2024
Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou, China.
Background: Gastric cancer (GC) is one of the leading contributors to global malignancies incidence and mortality worldwide. Advanced GC had a relatively poor prognosis. The emerging of targeted therapy improved the survival and prognosis of GC patients.
View Article and Find Full Text PDFOncol Res
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View Article and Find Full Text PDFIndian J Pathol Microbiol
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Background: Investigation of a potential prognostic marker expressed in non-small cell lung cancer (NSCLC) can help patients benefit from new target therapeuticmodalities.
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