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

Brandon, Jimi L.; Conti, Claudio J.; Goldstein, Lawrence S.B.; DiGiovanni, John; Gimenez-Conti, Irma

doi:10.1177/0192623309344203

Cited by 8 publications

(7 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have reported increased cellular proliferation in cultured cells (reviewed in Burdick et al, 2003; IARC, 2010) and animal models (Brandon et al, 2009; Wester et al, 2012) in response to BaP exposure. Studies in murine and human cells have clearly shown that BaP induces apoptosis in these cell models (reviewed in IARC, 2010).…”

Section: Genomics Approaches (Ra2 and Ra3)mentioning

confidence: 99%

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Moffat

Chepelev

Labib

et al. 2015

Critical Reviews in Toxicology

140

100

View full text Add to dashboard Cite

Toxicogenomics is proposed to be a useful tool in human health risk assessment. However, a systematic comparison of traditional risk assessment approaches with those applying toxicogenomics has never been done. We conducted a case study to evaluate the utility of toxicogenomics in the risk assessment of benzo[a]pyrene (BaP), a well-studied carcinogen, for drinking water exposures. Our study was intended to compare methodologies, not to evaluate drinking water safety. We compared traditional (RA1), genomics-informed (RA2) and genomics-only (RA3) approaches. RA2 and RA3 applied toxicogenomics data from human cell cultures and mice exposed to BaP to determine if these data could provide insight into BaP's mode of action (MOA) and derive tissue-specific points of departure (POD). Our global gene expression analysis supported that BaP is genotoxic in mice and allowed the development of a detailed MOA. Toxicogenomics analysis in human lymphoblastoid TK6 cells demonstrated a high degree of consistency in perturbed pathways with animal tissues. Quantitatively, the PODs for traditional and transcriptional approaches were similar (liver 1.2 vs. 1.0 mg/kg-bw/day; lung 0.8 vs. 3.7 mg/kg-bw/day; forestomach 0.5 vs. 7.4 mg/kg-bw/day). RA3, which applied toxicogenomics in the absence of apical toxicology data, demonstrates that this approach provides useful information in data-poor situations. Overall, our study supports the use of toxicogenomics as a relatively fast and cost-effective tool for hazard identification, preliminary evaluation of potential carcinogens, and carcinogenic potency, in addition to identifying current limitations and practical questions for future work.

show abstract

Section: Genomics Approaches (Ra2 and Ra3)mentioning

confidence: 99%

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Moffat

Chepelev

Labib

et al. 2015

Critical Reviews in Toxicology

140

100

View full text Add to dashboard Cite

show abstract

“…We have also recorded in vivo images of a cheek pouch in a hamster model of oral cancer [6]. Images of a visible lesion (diagnosed by histology as squamous cell carcinoma) were acquired over a 2 × 2 mm field of view with an average power of ~3 mW on the sample and a laser repetition rate of 10 kHz.…”

mentioning

confidence: 99%

High-speed multispectral fluorescence lifetime imaging implementation for in vivo applications

et al. 2010

View full text Add to dashboard Cite

Fluorescence lifetime imaging microscopy (FLIM) offers a noninvasive approach for characterizing the biochemical composition of biological tissue. In recent years, there has been an increasing interest in the application of multispectral FLIM for medical diagnosis. Central to the clinical translation of FLIM technology is the development of robust, fast, and cost-effective FLIM instrumentation suitable for in vivo tissue imaging. Unfortunately, the predominant multispectral FLIM approaches suffer from limitations that impede the development of high-speed instruments for in vivo applications. We present a cost-effective scanning multispectral FLIM implementation capable of achieving pixel rates on the order of tens of kilohertz, which will facilitate the evaluation of FLIM for in vivo applications.

show abstract

“…Based on previously published grading scales [25,26], a five-point dysplasia scale was utilized. H&E-stained specimens were submitted to a board-certified veterinary pathologist (S.E.K.)…”

Section: Methodsmentioning

confidence: 99%

Fluorescence Identification of Head and Neck Squamous Cell Carcinoma and High-Risk Oral Dysplasia With BLZ-100, a Chlorotoxin-Indocyanine Green Conjugate

Baik

Hansen

Knoblaugh

et al. 2016

JAMA Otolaryngol Head Neck Surg

View full text Add to dashboard Cite

Importance Surgical cure of head and neck squamous cell carcinoma (HNSCC) remains hampered by inadequately resected tumors and poor recognition of lesions with malignant potential. BLZ-100 is chlorotoxin-based tumor targeting agent which has not yet been studied in HNSCC. Objective To evaluate BLZ-100 uptake in models of HNSCC and oral dysplasia. Design Observational study (including sensitivity/specificity analysis) of BLZ-100 uptake in an orthotopic xenograft mouse model of HNSCC and a carcinogen-induced dysplasia model of hamster cheek pouches. Setting Research laboratory Participants NSG mice, Golden Syrian hamsters Interventions Various HNSCC xenografts were established in the tongues of NSG mice. BLZ-100 was intravenously injected and fluorescence uptake was measured. To induce dysplasia, the carcinogen DMBA was applied to the cheek pouch of Golden Syrian hamsters for 9–16 weeks. BLZ-100 was subcutaneously injected and fluorescence uptake was measured. Main Outcomes and Measures The signal-to-background ratio (SBR) of BLZ-100 was measured in tumor xenografts. To calculate the sensitivity and specificity of BLZ-100 uptake, a digital grid was placed over tissue sections and correlative histologic sections to discretely measure fluorescence intensity and presence of tumor; a receiver operating characteristic (ROC) curve was then plotted. In the hamster dysplasia model, cheeks were graded according to dysplasia severity. The SBR of BLZ-100 was compared among dysplasia grades. Results In HNSCC xenografts, BLZ-100 demonstrated an overall signal-to-background ratio (SBR) of 2.51 +/− 0.47 SD. The ROC curve demonstrated an area under the curve (AUC) of 0.889; a SBR of 2.5 corresponded to 92% sensitivity and 74% specificity. When this analysis was focused on the tumor and non-tumor interface, the AUC increased to 0.971; a SBR of 2.5 corresponded to 95% sensitivity and 91% specificity. DMBA treatment of hamster cheek pouches generated lesions representing all grades of dysplasia. The SBR of high-grade dysplasia was significantly greater than that of mild-to-moderate dysplasia (2.31 +/− 0.71 SD versus 1.51 +/− 0.34 SD, p=0.006). Conclusions and Relevance BLZ-100 is a sensitive and specific marker of HNSCC, and can distinguish high-risk from low-risk dysplasia. BLZ-100 has the potential to serve as an intraoperative guide for tumor margin excision and identification of pre-malignant lesions.

show abstract

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

Cited by 8 publications

References 28 publications

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water

High-speed multispectral fluorescence lifetime imaging implementation for in vivo applications

Fluorescence Identification of Head and Neck Squamous Cell Carcinoma and High-Risk Oral Dysplasia With BLZ-100, a Chlorotoxin-Indocyanine Green Conjugate

Contact Info

Product

Resources

About