@article{malarkey_parker_turman_scott_paules_collins_maronpot_2005, title={Microarray data analysis of mouse neoplasia}, volume={33}, ISSN={["1533-1601"]}, DOI={10.1080/01926230590888315}, abstractNote={ Microarray gene expression analysis offers great promise to help us understand the molecular events of experimental carcinogenesis, but have such promises been fulfilled? Studies of gene expression profiles of rodent are being published and demonstrate that yes, indeed, gene array data is furthering our understanding of tumor biology. Recent studies have identified differentially expressed genes in rodent mammary, colon, lung, and liver tumors. Although relatively few genes on the rodent arrays have been fully characterized, information has been generated to better identify signatures of histologic type and grade, understand invasion and metastasis, identify candidate biomarkers of early development, identify gene networks in carcinogenesis, understand responses to therapy, and decifer overlap with molecular events in human cancers. Data from mouse lung, mammary gland, and liver tumor studies are reviewed as examples of how to approach and interpret gene array data. Methods of gene array data analysis were also applied for discovery of genes involved in the regression of mouse liver tumors induced by chlordane, a nongenotoxic murine hepatocarcinogen. Promises are beginning to be fulfilled and it is clear that pathologists and toxicologists, in collaboration with molecular biologists, bioinformatists, and other scientists are making great strides in the design, analysis, and interpretation of microarray data for cancer studies. }, number={1}, journal={TOXICOLOGIC PATHOLOGY}, author={Malarkey, DE and Parker, JS and Turman, CA and Scott, AM and Paules, RS and Collins, J and Maronpot, RR}, year={2005}, pages={127–135} }
 @article{hailey_haseman_bucher_radovsky_malarkey_miller_nyska_maronpot_1998, title={Impact of Helicobacter hepaticus infection in B6C3F(1) mice from twelve national toxicology program two-year carcinogenesis studies}, volume={26}, ISSN={["0192-6233"]}, DOI={10.1177/019262339802600503}, abstractNote={ Male and female B6C3F1 mice from 12 National Toxicology Program (NTP) 2-yr carcinogenesis studies were found to be infected with Helicobacter hepaticus. Many of the male mice from 9 of these studies had an associated hepatitis (affected studies). Helicobacter hepaticus has been reported to be associated with an increased incidence of hepatitis and hepatocellular neoplasms in the A/JCr male mouse. We attempted to determine if the data from the Helicobacter-affected NTP B6C3F1 mouse studies were compromised and unsuitable for cancer hazard identification. The incidences of neoplasms of the liver (both hepatocellular and hemangiosarcoma) but not of other organs in control male B6C3F1 mice were increased in affected studies as compared with control males from unaffected studies. The increased incidence of hepatocellular neoplasms was observed in those males exhibiting H. hepaficus-associated hepatitis. Other observations further differentiated control male mice from affected and unaffected studies. H- ras codon 61 CAA to AAA mutations were less common in liver neoplasms from males from affected studies as compared with historical and study controls. In addition, increases in cell proliferation rates and apoptosis were observed in the livers of male mice with H. hepaticus-associaled hepatitis. These data support the hypothesis that the increased incidence of liver neoplasms is associated with H. hepaticus and that hepatitis may be important in the pathogenesis. Therefore, interpretation of carcinogenic effects in the liver of B6C3F1 mice may be confounded if there is H. hepaticus-associaled hepatitis. }, number={5}, journal={TOXICOLOGIC PATHOLOGY}, author={Hailey, JR and Haseman, JK and Bucher, JR and Radovsky, AE and Malarkey, DE and Miller, RT and Nyska, A and Maronpot, RR}, year={1998}, pages={602–611} }
 @article{kim_porter_foley_maronpot_smart_1997, title={Evidence that mirex promotes a unique population of epidermal cells that cannot be distinguished by their mutant Ha ras genotype}, volume={20}, DOI={10.1002/(SICI)1098-2744(199709)20:1<115::AID-MC13>3.0.CO;2-4}, abstractNote={Mirex is a potent tumor promoter in 7,12‐dimethylbenz[a]anthracene (DMBA)–initiated female CD‐1 mouse skin. Like 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA), mirex promotes papillomas that have a Ha‐ras mutation; however, unlike TPA promotion, mirex promotion does not involve a general hyperplastic response. We used proliferating cell nuclear antigen (PCNA) and 5‐bromo‐2′‐deoxyuridine (BrdU) immunohistochemical staining to further examine the proliferative capacity of mirex. The numbers of PCNA‐ and BrdU‐positive epidermal S‐phase cells were highly concordant in all treatment groups. Unlike a single application of TPA, a single application of mirex had little or no effect on the number of S‐phase epidermal cells, and chronic application of mirex to mouse skin produced only minimal increases in S‐phase cells. Moreover, mirex did not significantly alter the growth of BALB/MK‐2 keratinocytes in media containing either 0.05 or 1.2 mM Ca++. These results suggest that mirex may have highly specific effects on the proliferation of initiated cells and support the existence of a unique mirex mechanism and/or distinct population of mirex‐promotable mutant Ha‐ras epidermal cells. To begin to address this issue of a distinct population of mirex‐promotable mutant Ha‐ras cells, we conducted a tandem experiment in which DMBA‐initiated mice were treated twice weekly with a maximal promoting dose of mirex. Then, when the number of papillomas reached a plateau, these same mice were treated twice weekly with a maximal promoting dose of TPA. Mice treated with mirex developed a maximum of 6.4 papillomas/mouse. These mice were then promoted with TPA, which produced 8.9 additional papillomas/mouse for a total of 15.3 papillomas/mouse. The maximum tumor yields from other groups of mice treated with only TPA or mirex were 9.8 and 7.3 papillomas/mouse, respectively. Therefore, under these tandem conditions, tumor yields were additive, indicating that there are at least two distinct populations of mutant Ha‐ras cells: one promoted by mirex and the other by TPA. Mol. Carcinog. 20:115–124, 1997. © 1997 Wiley‐Liss, Inc.}, number={1}, journal={Molecular Carcinogenesis}, author={Kim, T. W. and Porter, K. L. and Foley, J. F. and Maronpot, R. R. and Smart, Robert}, year={1997}, pages={115–124} }
 @article{davis_almekinder_flagler_travlos_wilson_maronpot_1997, title={Ovarian luteal cell toxicity of ethylene glycol monomethyl ether and methoxy acetic acid in vivo and in vitro}, volume={142}, ISSN={["0041-008X"]}, DOI={10.1006/taap.1996.8035}, abstractNote={These studies define the site and mechanisms of reproductive toxicity of ethylene glycol monomethyl ether (EGME) in a nongravid female animal model using in vivo and in vitro methods. In vivo studies assessed vaginal cytology and histology, ovarian histology, and serum hormones in 80- to 90-day-old, adult, regularly cycling, female Sprague-Dawley rats treated daily with EGME or vehicle by oral gavage. Dose-response and time-course studies (four to nine rats per group per treatment) determined that 300 mg/kg EGME suppressed cyclicity without systemic toxicity within 3 to 8 days, and doses less than 100 mg/kg had no effect. Pathogenesis studies (six to nine rats per time and treatment) determined that 300 mg/kg EGME elevated serum progesterone within 32 hr after dosing, while serum estradiol, FSH, LH, and prolactin remained at baseline levels. In EGME-treated rats, cyclicity was suppressed, ovulation was inhibited, and corpora lutea were hypertrophied. Thus, EGME appeared to target the ovarian luteal cell. To further examine the toxicity in vitro, luteal cells were recovered from 23-day-old, hCG-primed Sprague-Dawley rats and treated with 0-10 mM methoxy acetic acid (MAA), the proximate toxic metabolite of EGME. MAA (1-10 mM) maintained elevated progesterone levels as production declined in untreated cells at 24 and 48 hr of culture. Progesterone production was maintained independent of LH-stimulated cAMP levels. MAA decreased ATP, but only at 48 hr and at 2.5 mM or greater concentrations. Thus, these studies establish that the ovarian luteal cell is a target of EGME and MAA in vivo and in vitro and that the effect on luteal cell progesterone production is likely independent of LH-stimulated cAMP pathways.}, number={2}, journal={TOXICOLOGY AND APPLIED PHARMACOLOGY}, author={Davis, BJ and Almekinder, JL and Flagler, N and Travlos, G and Wilson, R and Maronpot, RR}, year={1997}, month={Feb}, pages={328–337} }