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Titolo:
Frequency and molecular analysis of hprt mutations induced by estradiol inChinese hamster V79 cells
Autore:
Kong, LY; Szaniszlo, P; Albrecht, T; Liehr, JG;
Indirizzi:
Stehlin Fdn Canc Res, Houston, TX 77003 USA Stehlin Fdn Canc Res Houston TX USA 77003 Canc Res, Houston, TX 77003 USA Univ Texas, Med Branch, Dept Immunol & Microbiol, Galveston, TX 77555 USA Univ Texas Galveston TX USA 77555 ol & Microbiol, Galveston, TX 77555 USA
Titolo Testata:
INTERNATIONAL JOURNAL OF ONCOLOGY
fascicolo: 6, volume: 17, anno: 2000,
pagine: 1141 - 1149
SICI:
1019-6439(200012)17:6<1141:FAMAOH>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOSE-DEPENDENT DIFFERENCES; HUMAN LYMPHOCYTES-T; SYRIAN-HAMSTERS; MUTANT FREQUENCIES; CATECHOL ESTROGENS; BREAST-CANCER; V-79 CELLS; DNA-DAMAGE; GENE; INDUCTION;
Keywords:
estradiol; hprt; point mutations; deletions; V79 cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Liehr, JG Stehlin Fdn Canc Res, 1918 Chenevert, Houston, TX 77003 USA Stehlin Fdn Canc Res 1918 Chenevert Houston TX USA 77003 003 USA
Citazione:
L.Y. Kong et al., "Frequency and molecular analysis of hprt mutations induced by estradiol inChinese hamster V79 cells", INT J ONCOL, 17(6), 2000, pp. 1141-1149

Abstract

The natural hormone estradiol (E-2) induces tumors in rodents and various types of DNA damage in vitro, and in vivo, but has not been mutagenic in bacterial or mammalian assays. Recent reports of chromosomal and genetic lesions induced by E-2 has led us to re-examine the mutation frequency and molecular alterations of the hypoxanthine-guanine phosphoribosyltransferase (hrpt) gene in Chinese hamster V79 cells. E-2 at both physiological and pharmacological concentrations (10(-11), 10(-10), and 10(-7), 10(-6) M) significantly increased the mutation frequency of the hrpt gene by 2.57-, 3.35-, 2.63-, and 8.78-fold, respectively, compared to the controls, while 10(-13), 10(-12), 10(-9), or 10(-8) M E-2 induced little change (less than or equal to0.93-fold). PCR and a molecular analysis of the hprt coding sequence identified genetic lesions in the cDNA and/or genomic DNA in 15 of the 21 pickedE-2-induced mutants (71%). Simple base substitutions, such as T-->G or T-->A transversions, were the most common mutations (8/21 or 38%) and frequently occurred at 122 bp or 407 bp of the hprt coding sequence. Deletion mutations were detected in 6 of the 21 clones (29%). An A-->G and a C-->T transition and a four-base insertion (TATT) were identified each in one mutant clone. A RT-PCR analysis demonstrated an abundant expression of the estrogen receptor-alpha (ER alpha). However, ICI 182,780, an antagonist of ERa, acted in an additive manner with E-2 and increased the hrpt mutation frequency. In conclusion, E-2 induces a low frequency of mutations (deletions and point mutations) in V79 cells, which is consistent with the weak carcinogenic activity of this hormone. The mutagenic effects of E-2 in V79 cells are notmediated by the ER alpha..

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Documento generato il 25/11/20 alle ore 18:36:40