@article{youn_kim_ahn_kim_park_ryu_2009, title={Regulation of iron metabolism-related genes in diethylnitrosamine-induced mouse liver tumors}, volume={184}, ISSN={["1879-3169"]}, DOI={10.1016/j.toxlet.2008.11.002}, abstractNote={It has been suggested that the altered iron metabolism in liver tumors, characterized by the iron-deficient phenotype, is of importance for tumor growth. This study was performed to elucidate the mechanisms underlying iron deficiency in liver tumors by examining how the liver tumor development affects the expression of iron metabolism-related genes. Iron metabolism reference values were analyzed in the sera of diethylnitrosamine-induced hepatocellular adenoma-bearing mice. Expression of iron metabolism-related genes was analyzed in adenomas and surrounding non-tumor tissues, and a subgroup of adenoma-bearing mice loaded with iron 72 h before sacrifice. Iron content of the adenoma tissues was 2.0–2.5-fold lower compared to surrounding and age-matched control tissues. There was no significant difference in serum iron levels between the adenoma-bearing and control mice, while the adenoma-bearing mice exhibited a 2.4-fold lower level of serum transferrin saturation. Expression of iron metabolism-related genes was dysregulated in the adenomas. Iron loading affected protein expression similarly in the adenomas and surrounding tissues suggesting that iron-responsive regulation of the proteins was not impaired. However, the mRNA expression for ceruloplasmin and divalent metal transporter 1 (DMT1) IRE(+) in the adenomas was altered independently of iron status, and the dysregulation may contribute to diminished iron content. These findings suggest that diethylnitrosamine-induced liver adenoma-bearing mice have abnormal iron metabolism and that dysregulation of iron metabolism-related genes contributes to iron deficiency in the adenomas.}, number={3}, journal={TOXICOLOGY LETTERS}, author={Youn, Pilju and Kim, Soohee and Ahn, Jin Hee and Kim, Yongbaek and Park, Jung-Duck and Ryu, Doug-Young}, year={2009}, month={Feb}, pages={151–158} }
 @article{ryu_hodgson_1999, title={Constitutive expression and induction of CYP1B1 mRNA in the mouse}, volume={13}, ISSN={["1095-6670"]}, DOI={10.1002/(SICI)1099-0461(1999)13:5<249::AID-JBT4>3.0.CO;2-L}, abstractNote={Previous studies appeared to indicate that CYP1B1 was not constitutively expressed in mouse liver. In our laboratory, we demonstrated using aromatic hydrocarbon‐responsive receptor knock‐out (AHR––/–) mice that both piperonyl butoxide (PBO) and acenaphtyhlene (ACN) are AHR‐independent inducers of murine CYP1A2 and CYP1B1 mRNA. In the current study, we demonstrate both constitutive levels and induction of CYP1B1 in mouse liver. The induction of CYP1B1 mRNA by PBO or ACN was higher in DBA/2 (Ahrd) than in C57BL/6 (Ahrb−1) mice, while 3‐methylcholanthrene induced CYP1B1 more in C57BL/6 than in DBA/2 mice. These results suggest that CYP1B1 may also be induced by more than one mechanism. In addition, constitutive expression of CYP1B1 was detected in liver, kidney, and lung of untreated C57BL/6 mice. There was no gender difference in CYP1B1 expression; however, in C57BL/6 mice, the kidney contained less CYP1B1 than either liver or lung. © 1999 John Wiley & Sons, Inc. J Biochem Toxicol 13: 249–251, 1999}, number={5}, journal={JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY}, author={Ryu, DY and Hodgson, E}, year={1999}, pages={249–251} }
 @article{ryu_levi_hodgson_1997, title={Regulation of hepatic CYP1A isozymes by piperonyl butoxide and acenaphthylene in the mouse}, volume={105}, ISSN={["1872-7786"]}, DOI={10.1016/S0009-2797(97)00035-5}, abstractNote={The regulation of CYP1A1 and CYP1A2 isozymes by piperonyl butoxide (PBO) and acenaphthylene (ACN) was studied in the liver of male C57BL/6 and DBA/2 mice. These two cytochrome P450 genes are known to be regulated by the aromatic hydrocarbon-responsive receptor (AHR); however, it has been suggested that CYP1A2 is also induced by an AHR-independent mechanism. In this study, PBO induced hepatic CYP1A1 considerably more in C57BL/6 (Ahrb-I) than in DBA/2 (Ahrd) mice. In addition, the superinduction of CYP1A1 in wildtype hepa1c1c7 cells, which is AHR-dependent, resulted from PBO and cycloheximide treatment of the cells. In other studies in this laboratory using AHR knock-out (AHR-/-) mice, a hybrid of 129/SV and C57BL/6 strains, no induction of CYP1A1 occurred with PBO or ACN. [D.-Y. Ryu, P.E. Levi, P. Fernandez-Salguero, F.J. Gonzalez, E. Hodgson, Mol. Pharmacol., 50 (1996) 443-446.] ACN, however, did not induce CYP1A1 under the experimental conditions used. These results suggest that PBO, but not ACN, induces CYP1A1 through a weak activation of AHR. On the other hand, hepatic CYP1A2 mRNA and hnRNA were induced by PBO in both C57BL/6 and DBA/2 strains, but were not induced by ACN, a strong inducer of CYP1A2 in the B6C3F1 strain. However, both PBO and ACN induced CYP1A2 in AHR-/- mice. It is assumed, therefore, that the transcriptional induction of CYP1A2 by PBO and ACN is AHR-independent. In addition, the induction of CYP1A2 by ACN depends upon the strain of mice. Immunohistochemical studies for CYP1A1/CYP1A2 apoproteins showed that PBO induced CYP1A1/CYP1A2 around the central veins as did 3-methylcholanthrene (3-MC). The induction of CYP1A1/CYP1A2 by ACN, however, was not observed, consistent with the northern blot results.}, number={1}, journal={CHEMICO-BIOLOGICAL INTERACTIONS}, author={Ryu, DY and Levi, PE and Hodgson, E}, year={1997}, month={Jun}, pages={53–63} }
 @article{falls_ryu_cao_levi_hodgson_1997, title={Regulation of mouse liver flavin-containing monooxygenases 1 and 3 by sex steroids}, volume={342}, ISSN={["0003-9861"]}, DOI={10.1006/abbi.1997.9965}, abstractNote={Based on enzyme activity, protein levels, and mRNA levels, we have previously demonstrated the female-predominant, female-specific, and gender-independent expression in mouse liver of FMO forms 1, 3, and 5, respectively. This study investigated the roles of testosterone, 17 beta-estradiol, and progesterone in the regulation of hepatic FMOs. FMO expression was examined in gonadectomized CD-1 mice, normal CD-1 mice receiving hormonal implants, and gonadectomized mice receiving various hormonal treatments. Following castration of males, hepatic FMO activity levels were significantly increased and serum testosterone levels significantly decreased; however, administration of physiological levels of testosterone to castrated animals returned FMO activity and testosterone concentrations to control levels. When sexually intact and ovariectomized female mice were treated with testosterone, their hepatic FMO activity levels were reduced to those of their male counterparts, concomitant with high serum testosterone levels. In males, castration dramatically increased FMO3 and FMO1 expression, and testosterone replacement to castrated males resulted in ablation of FMO3 expression. In addition, testosterone administration to females (sexually intact and gonadectomized animals) reduced FMO1 expression and obviated FMO3 expression. In females, ovariectomy alone slightly reduced FMO activity, indicative of a possible stimulatory role of female sex steroids; however, female FMO isozyme expression was relatively unchanged, and hormone replacement therapy to ovariectomized females had no discernible effect. In males and females, FMO5 levels were unaffected by gonadectomy or hormone administration, thus indicating a sex hormone-independent mechanism of regulation for this isoform. Interestingly, FMO1 protein levels were increased in sexually intact males following treatment with 17 beta-estradiol; however, only a slight increase in FMO3 protein level was observed. No positive hormone effectors of female FMO expression were identified.}, number={2}, journal={ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS}, author={Falls, JG and Ryu, DY and Cao, Y and Levi, PE and Hodgson, E}, year={1997}, month={Jun}, pages={212–223} }