Biologist — Genetic and Molecular Toxicology

Dayton Petibone, Ph.D.
(870) 543-7121
NCTRResearch@fda.hhs.gov  

Back to NCTR Principal Investigators page

About  |  Publications 

Background

Dr. Dayton Petibone majored in biology with a minor in chemistry during his B.S. degree studies at Northern Michigan University. He continued to pursue a M.S. research degree at Northern Michigan University, which focused on identifying DNA response elements involved in hormonal regulation of insect-cuticle protein gene expression. Dr. Petibone conducted his Ph.D. work at the University of Arkansas at Little Rock. His Ph.D. research concentrated on understanding the effect that tumor suppressor p53 functional status has on cytotoxicity and genotoxicity in human B-lymphoblastoid cells exposed to an oxidized graphene nanomaterial.    

During his career, Dr. Petibone worked for many years in the Department of Biological Sciences at Wayne State University. At Wayne State, he participated in or supervised several human, rodent, and nonhuman-primate studies using classic and molecular cytogenetic techniques. These studies included, among other research efforts:

• Investigating retrospective radiation biodosimetry.
• Developing methods for applying human fluorescence in situ hybridization (FISH) probes to analysis of rhesus macaque chromosomes.
• Evaluating methylphenidate induced genotoxicity.

In addition, he was involved in training and working with graduate students, undergraduate students, and visiting scientists conducting a variety of genotoxicity and gene-expression experiments designed to identify biomarkers for radiation dosimetry. Since 2009, Dr. Petibone has worked as a biologist at NCTR in the Division of Genetic and Molecular Toxicology. In the division, he investigates p53 function in the genotoxicity induced by agents of interest to the FDA. In addition, his research efforts include the development, modernization, and validation of in vitro gene-mutation tests for higher-throughput assessments relevant to both human exposures and to carcinogenesis. Recently, Dr. Petibone was awarded the 2016 NCTR “Excellence in Laboratory Science Award” for participating in a workgroup that established human whole-genome sequencing at NCTR and characterized the genome of cell lines with different p53 functional status that are commonly used in genetic toxicology. He also received the 2016 FDA “Group Recognition Award” for participating in characterization of a novel gene mutation assay for regulatory safety assessments.

Research Interests

Investigating the effect p53 functional status has in toxicity is an overarching subject in Dr. Petibone’s research. The p53 protein activates gene expression and cell-signaling pathways:

• in response to stress stimuli
• to correct DNA damage
• to suppress tumor formation.

Constant exposure to endogenous and exogenous stressors can inflict damage to cells within the human body. This damage includes DNA mutation that can result in disease or cancer. To maintain a healthy status, cells must have a way to identify and correct DNA damage, so as not to transmit corrupted genetic information to subsequent generations of daughter cells. Following DNA damage, activation of p53-mediated signaling pathways has three primary cellular outcomes to restore stability: 1) cell cycle arrest with DNA repair and cell cycle restart, 2) cell senescence, or 3) apoptosis. However, if not corrected through p53-regulated pathways, mutated and proliferating pre-neoplastic cells might result in tumors. The p53 gene is one of the most studied targets in cancer research, and it is known that over half of the tumors which arise in humans harbor a mutation in the p53 gene. Evaluating the role of p53 in cellular responses to potentially toxic agents can provide useful information as to the level of toxicity and the mode-of-action for an agent, especially as p53 functional status relates to DNA damage.

Structural chromosome damage is a hallmark of cancer and assessing chromosome damage is critical when evaluating the potential genotoxicity of a suspected test agent. Whole-chromosome fluorescence in situ hybridization (FISH) of metaphase cells provides a means for rapidly and accurately analyzing structural chromosome aberrations with single-cell level resolution. FISH-painted metaphase cells labeled as described below allows for higher-throughput analysis compared to classic cytogenetic methods, and allows for identifying chromosome exchanges.

• chromosomes 1, 2, and 4 labeled red
• chromosomes 3, 5, and 6 labeled green
• all chromosomes counter-stained blue.

These genetic exchanges include identifying reciprocal/non-reciprocal chromosome translocations, insertion events, and dicentric chromosomes to evaluate genotoxicity and predict carcinogenesis. Dr. Petibone specializes in developing and applying molecular FISH techniques for assessing the ability of potential genotoxicants to induce structural chromosome damage.

Gene-mutation tests are vital tools used for detecting genotoxicity as a means to predict carcinogenic potential. Despite their importance in making regulatory decisions, there are inherent limitations to the current mammalian in vitro gene-mutation assays. A main shortcoming of many in vitro gene-mutation assays is the use of nucleotide-metabolism genes as the mutagenesis target — genes which are not involved in carcinogenesis but serve as a proxy for cancer-relevant tumor-suppressor gene mutagenesis. Additionally, gene-mutation analysis often depends on extended time periods of mutant-clonal expansion, making the gene-mutation assays laborious and with limited adaptability for high-throughput screening.  Recently, Dr. Petibone has undertaken research to advance the development, modernization, and validation of existing gene-mutation assays specifically for high-throughput analysis, and the innovation of new gene-mutation assays that are relevant to human cancer.

Professional Societies/National and International Groups

Environmental Mutagen and Genomics Society
Member
2012 – 2015

Select Publications

p53-Competent Cells and p53-Deficient Cells Display Different Susceptibility to Oxygen Functionalized Graphene Cytotoxicity and Genotoxicity.
Petibone D.M., Mustafa T., Ding W., Bourdo S., Lafont A., Watanabe F., Casciano D., Morris S.M., Dobrovolsky V., and Biris A.
Journal of Applied Toxicology. 2017, doi: 10.1002/jat.3472. [Epub ahead of print]
 

In Vivo Rat T-Lymphocyte Pig-A Assay: Detection and Expansion of Cells Deficient in the GPI-Anchored CD48 Surface Marker for Analysis of Mutation in the Endogenous Pig-A Gene.
Dobrovolsky V., Revollo J., Petibone D., and Heflich R.
Methods Mol Biol. 2017, 1641:143-160.
 

The Role of Surface Chemistry in the Cytotoxicity Profile of Graphene. 
Majeed W., Bourdo S., Petibone D., Saini V., Vang K.B., Nima Z.A., Alghazali K.M., Darrigues E., Ghosh A., Watanabe F., Casciano D., Ali S.F., and Biris A.S.
J Appl Toxicol. 2017, 37 (4): 462-470.
 

Autophagy Function and its Relationship to Pathology, Clinical Applications, Drug Metabolism, and Toxicity. 
Petibone D., Majeed W., and Casciano D.
Journal of Applied Toxicology. 2016, 37 (1): 23-37.
 

Whole Genome and Normalized Mrna Sequencing Reveal Genetic Status of TK6, WTK1, and NH32 Human B-Lymphoblastoid Cell Lines. 
Revollo J., Petibone D., McKinzie P., Knox B., Morris S.M., Ning B., and Dobrovolsky V.N.
Mutat Res Genet Toxicol Environ Mutagen. 2016, 795:60-9.
 

Confirmation of Pig-A Mutation in Flow Cytometry-Identified CD48-Deficient T-Lymphocytes Derived from Spleens of ENU-Treated F344 Rats. 
Revollo J., Pearce M., Petibone D., Mittelstaedt R., and Dobrovolsky V.
Mutagenesis. 2015, 30 (3): 315-324.
 

Chromosome Painting of Mouse Peripheral Blood and Spleen Tissues. (Book Chapter)
Petibone D., Tucker J., and Morris S.
In Gaivão I. and Sierra L.M. (Eds.) Genotoxicity and DNA Repair: A Practical Approach.
Methods in Pharmacology and Toxicology. 2014, 141-158.
 

p53 Alters the Biologically Effective Dose, Cytotoxicity, and Genotoxicity for Oxidized Graphene in Human Lymphoblastoid Cells. 
Petibone D., Mustafa T., Ding W., Bourdo S., Lafont A., Watanabe F., Casciano D., Morris S., Dobrovolsky V., and Biris A.
J Toxicology. 2014 Jun 20.
 

Toxicity and Efficacy of Carbon Nanotubes and Graphene: The Utility of Carbon-Based Nanoparticles in Nanomedicine. 
Zhang Y., Petibone D., Xu Y., Mahmood M., Karmakar A., Casciano D., Ali S., and Biris A.S.
Drug Metab Rev. 2014, 46(2):232-46.
 

In Vivo Genotoxicity of Furan in F344 Rats at Cancer Bioassay Doses. 
Ding W., Petibone D., Latendresse J.R., Pearce M.G., Muskhelishvili L., White G.A., Chang C.-W., Mittelstaedt R.A., Shaddock J.G., McDaniel L.P., Doerge D.R., Morris S.M., Chen J., Manjanatha M.G., Aidoo A., and Heflich R.H.
Toxicology and Applied Pharmacology. 2012, 261(2): 164-171.
 

The Genetic Toxicity of Methylphenidate: A Review of the Current Literature. 
Morris S.M., Petibone D., Lin W.-J., Chen J.J., Vitiello B., Witt K.L., and Mattison D.R.
Journal Of Applied Toxicology. 2012, 32(10): 756-764.
 

Evaluation of P53 Genotype on Gene Expression in the Testis, Liver and Heart from Male C57BL/6 Mice. 
Petibone D.M., Kulkarnia R., Changb C.W., Chen J.J., and Morrisa S.M.
Transgenic Res. 2012, 21:257–263.
 

Pubertal Delay in Male Non-Human Primates (Macaca mulatta) Treated with Methylphenidate. 
Mattison D.R., Plant T.M., Lin H.-M., Chen H.-C., Chen J.J., Twaddle N.C., Doerge D., Slikker W. Jr., Patton R.E., Hotchkiss C.E., Callicott R.J., Schrader S.M., Turner T.W., Kesner J.S., Vitiello B., Petibone D.M., and Morris S.M.
Proc Natl Acad Sci U S A. 2011, 108(39):16301-6.
 

Effect of P53 Genotype on Gene Expression and DNA Adducts in ENU-Exposed Mice. 
Kulkarni R., Petibone D., Chang C.-W., Chen J.J., Tolleson W.H., Melchior W.B. Jr., Churchwell M.I., Beland F.A., and Morris S.M.
General, Applied and Systems Toxicology. 2011.
 

Oligonucleotide Immobilization using 10-(carbomethoxy)Decyl-Dimethylchlorosilane for mRNA Isolation and cDNA Synthesis on a Microfluidic Chip. 
Hughes-Chinkhota C.N., Banda M., Smolinski J.M., Thomas R.A., Petibone D.M., Tucker J.D., and Auner G.W.
Sensors and Actuators B: Chemical. 2011, 155 (2): 437-45.
 

Cytogenetic Assessment of Methylphenidate Treatment in Pediatric Patients Treated for Attention Deficit Hyperactivity Disorder. 
Tucker J.D., Suter W., Petibone D., Thomas R.A., Bailey N.L., Zhou Y., Zhao Y., Muniz R., and Kumar V.
Mutation Research. 2009, 677(1-2):53-8.
 

The Genetic Toxicology of Methylphenidate Hydrochloride in Non-Human Primates. 
Morris S.M., Dobrovolsky V.N., Shaddock J.G., Mittelstaedt R.A., Bishop M.E., Manjanatha M.G., Shelton S.D., Doerge D.R., Twaddle N.C., Chen J.J., Lin C.J., Paule M.G., Slikker W. Jr., Hotchkiss C.E., Petibone D., Tucker J.D., and Mattison D.R.
Mutation Research. 2009, 673(1):59-66.
 

Routine Diagnostic X-ray Examinations and Increased Frequency of Chromosome Translocations Among United States Radiologic Technologists. 
Sigurdson A.J., Bhatti P., Preston D.L., Doody M.M., Kampa D., Alexander B.H., Petibone D., Yong L.C., Edwards A.A., and Tucker J.D.
Cancer Research. 2008, 68 (21): 8825-31.
 

Technique for Culturing Macaca mulatta Peripheral Blood Lymphocytes for Fluorescence in Situ Hybridization of Whole Chromosome Paints. 
Petibone D.M., Morris S.M., Hotchkiss C.E., Mattison D.R., and Tucker J.D.
Mutation Research. 2008, 653:76-81.
 

Retrospective Biodosimetry among United States Radiologic Technologists. 
Bhatti P., Preston D.L., Doody M.M., Hauptmann M., Kampa D., Alexander B.H., Petibone D., Simon S.L., Weinstock R.M., Bouville A., Yong L.C., Freedman D.M., Mabuchi K., Linet M.S., Edwards A.A., Tucker J.D., and Sigurdson A.J. 
Radiation Research. 2007, 167(6):727-34.