BACKGROUND & AIMS: We showed previously that the peroxisome proliferators di(2-ethylhexyl)phthalate (DEHP), clofibrate, and 4-chloro-6-(2,3 xylidino)-2-pyrimidinylthio (N-beta-hydroxyl)acetamide (BR931) alter hepatic sex steroid metabolism and receptor expression during induction of hepatic hyperplasia and hepatocellular carcinoma (HCC) in rats. The aim of this study was to identify metabolic changes associated with cell growth during hyperplasia and HCC. METHODS: Hepatic hyperplasia was induced in male rats by a diet containing DEHP and clofibrate for 3-60 days. HCC was induced by feeding a diet containing BR931, a more potent hepatocarcinogen, for 10 months. RESULTS: Cholesterol biosynthesis was depressed in hyperplastic livers but increased in HCC. Glucose-6-phosphate dehydrogenase (G6PD) activity was inhibited in hyperplastic liver as well as in HCC, whereas malic enzyme activity increased severalfold. Protein and messenger RNA (mRNA) levels for both G6PD and malic enzyme increased in hyperplastic livers and HCC. mRNA levels for 3-hydroxy-3-methylglutaryl-coenzyme A reductase decreased in hyperplasia and increased in HCC, whereas low-density lipoprotein receptor mRNA increased in hyperplasia and decreased in HCC. CONCLUSIONS: Neoplastic cells acquire a growth advantage by their capacity to synthesize cholesterol and obtain reduced nicotinamide adenine dinucleotide phosphate by the malic enzyme pathway when G6PD activity is inhibited by peroxisome proliferators.
BACKGROUND & AIMS: We showed previously that the peroxisome proliferators di(2-ethylhexyl)phthalate (DEHP), clofibrate, and 4-chloro-6-(2,3 xylidino)-2-pyrimidinylthio (N-beta-hydroxyl)acetamide (BR931) alter hepatic sex steroid metabolism and receptor expression during induction of hepatic hyperplasia and hepatocellular carcinoma (HCC) in rats. The aim of this study was to identify metabolic changes associated with cell growth during hyperplasia and HCC. METHODS:Hepatic hyperplasia was induced in male rats by a diet containing DEHP and clofibrate for 3-60 days. HCC was induced by feeding a diet containing BR931, a more potent hepatocarcinogen, for 10 months. RESULTS:Cholesterol biosynthesis was depressed in hyperplastic livers but increased in HCC. Glucose-6-phosphate dehydrogenase (G6PD) activity was inhibited in hyperplastic liver as well as in HCC, whereas malic enzyme activity increased severalfold. Protein and messenger RNA (mRNA) levels for both G6PD and malic enzyme increased in hyperplastic livers and HCC. mRNA levels for 3-hydroxy-3-methylglutaryl-coenzyme A reductase decreased in hyperplasia and increased in HCC, whereas low-density lipoprotein receptor mRNA increased in hyperplasia and decreased in HCC. CONCLUSIONS: Neoplastic cells acquire a growth advantage by their capacity to synthesize cholesterol and obtain reduced nicotinamide adenine dinucleotide phosphate by the malic enzyme pathway when G6PD activity is inhibited by peroxisome proliferators.
Authors: Julia Kravchenko; Emanuela Corsini; Marc A Williams; William Decker; Masoud H Manjili; Takemi Otsuki; Neetu Singh; Faha Al-Mulla; Rabeah Al-Temaimi; Amedeo Amedei; Anna Maria Colacci; Monica Vaccari; Chiara Mondello; A Ivana Scovassi; Jayadev Raju; Roslida A Hamid; Lorenzo Memeo; Stefano Forte; Rabindra Roy; Jordan Woodrick; Hosni K Salem; Elizabeth P Ryan; Dustin G Brown; William H Bisson; Leroy Lowe; H Kim Lyerly Journal: Carcinogenesis Date: 2015-05-22 Impact factor: 4.944
Authors: Barbara Klotz; Susanne Kneitz; Martina Regensburger; Lena Hahn; Michael Dannemann; Janet Kelso; Birgit Nickel; Yuan Lu; William Boswell; John Postlethwait; Wesley Warren; Manfred Kunz; Ronald B Walter; Manfred Schartl Journal: Comp Biochem Physiol C Toxicol Pharmacol Date: 2017-11-21 Impact factor: 3.228
Authors: Kannan Badri Narayanan; Manaf Ali; Barry J Barclay; Qiang Shawn Cheng; Leandro D'Abronzo; Rita Dornetshuber-Fleiss; Paramita M Ghosh; Michael J Gonzalez Guzman; Tae-Jin Lee; Po Sing Leung; Lin Li; Suidjit Luanpitpong; Edward Ratovitski; Yon Rojanasakul; Maria Fiammetta Romano; Simona Romano; Ranjeet K Sinha; Clement Yedjou; Fahd Al-Mulla; Rabeah Al-Temaimi; Amedeo Amedei; Dustin G Brown; Elizabeth P Ryan; Annamaria Colacci; Roslida A Hamid; Chiara Mondello; Jayadev Raju; Hosni K Salem; Jordan Woodrick; A Ivana Scovassi; Neetu Singh; Monica Vaccari; Rabindra Roy; Stefano Forte; Lorenzo Memeo; Seo Yun Kim; William H Bisson; Leroy Lowe; Hyun Ho Park Journal: Carcinogenesis Date: 2015-06 Impact factor: 4.944
Authors: Josiah Ochieng; Gladys N Nangami; Olugbemiga Ogunkua; Isabelle R Miousse; Igor Koturbash; Valerie Odero-Marah; Lisa J McCawley; Pratima Nangia-Makker; Nuzhat Ahmed; Yunus Luqmani; Zhenbang Chen; Silvana Papagerakis; Gregory T Wolf; Chenfang Dong; Binhua P Zhou; Dustin G Brown; Anna Maria Colacci; Roslida A Hamid; Chiara Mondello; Jayadev Raju; Elizabeth P Ryan; Jordan Woodrick; A Ivana Scovassi; Neetu Singh; Monica Vaccari; Rabindra Roy; Stefano Forte; Lorenzo Memeo; Hosni K Salem; Amedeo Amedei; Rabeah Al-Temaimi; Fahd Al-Mulla; William H Bisson; Sakina E Eltom Journal: Carcinogenesis Date: 2015-06 Impact factor: 4.944
Authors: Ruiyin Chu; Hanjo Lim; Laura Brumfield; Hong Liu; Chris Herring; Peter Ulintz; Janardan K Reddy; Matthew Davison Journal: Mol Cell Biol Date: 2004-07 Impact factor: 4.272
Authors: Andrée M Vandermeeren; Carmen Elena Gómez; Cristina Patiño; Elena Domingo-Gil; Susana Guerra; Jose Manuel González; Mariano Esteban Journal: Virol J Date: 2008-09-15 Impact factor: 4.099
Authors: Maja M Grabacka; Anna Wilk; Anna Antonczyk; Paula Banks; Emilia Walczyk-Tytko; Matthew Dean; Malgorzata Pierzchalska; Krzysztof Reiss Journal: Front Endocrinol (Lausanne) Date: 2016-02-02 Impact factor: 5.555