title: Intracellular distribution of the antimutagenic enzyme MTH1 in the liver, kidney and testis of F344 rats and its modulation by cadmium.
abstract: Cellular distribution of the antimutagenic MTH1protein in the liver, kidney, and testis of Fischer rat was evaluated using the immunohistochemical staining with anti-MTH1 polyclonal antibody. The present investigation revealed a non-uniform distribution of MTH1 among cells and among the cytoplasmic, nuclear, and membranal structures of cells within a given tissue. A particularly strong expression of MTH1 was observed for the first time in the perinuclear acrosomic bodies of spermatocytes and in the acrosomic vesicles of sperm heads. Treatment of rats with a single sc dose of 20 micromol Cd(II)/kg body wt. produced histopathologic changes in these organs accompanied by redistribution of the cellular MTH1 protein between the cytoplasm and nuclei. The acute phase of Cd(II) toxicity, that in the liver and especially in the testes (but not in kidneys) led to cell necrosis, was accompanied by a characteristic decrease in the abundance of MTH1-expressing nuclei. Chronic toxicity without necrosis, persisting in the kidney over the entire 14-day study, as well as the survival and proliferation of cells, observed in the liver and testis after the necrotizing phase, were signified by increased number of nuclei expressing MTH1. Thus, unlike previous biochemical studies, immunohistochemistry managed to reveal alterations in the patterns of inter- and intracellular distribution of MTH1, associated apparently with the conditional changes in the dynamics of synthesis of nucleic acids, assisted by this protein.
authors.affiliation: Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, MD 21702-1201, USA. kasprzak@mail.ncifcrf.gov
authors.forename: K S
authors.initials: KS
authors.lastname: Kasprzak
authors.forename: Y
authors.initials: Y
authors.lastname: Nakabeppu
authors.forename: T
authors.initials: T
authors.lastname: Kakuma
authors.forename: Y
authors.initials: Y
authors.lastname: Sakai
authors.forename: K
authors.initials: K
authors.lastname: Tsuruya
authors.forename: M
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: J M
authors.initials: JM
authors.lastname: Ward
authors.forename: B A
authors.initials: BA
authors.lastname: Diwan
authors.forename: K
authors.initials: K
authors.lastname: Nagashima
authors.forename: B H
authors.initials: BH
authors.lastname: Kasprzak
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000378:metabolism*; D015153:Blotting, Western; D002104:Cadmium / Q000633:toxicity*; D002467:Cell Nucleus / Q000201:enzymology; D003593:Cytoplasm / Q000187:drug effects / Q000201:enzymology; D045643:DNA Repair Enzymes; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008854:Microscopy, Electron; D009928:Organ Specificity; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011755:Pyrophosphatases / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013737:Testis / Q000187:drug effects / Q000201:enzymology*
chemical_list: D016587:Antimutagenic Agents; C000616635:Nudt1 protein, rat; D002104:Cadmium; D010744:Phosphoric Monoester Hydrolases; D011755:Pyrophosphatases; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes