Frequency and molecular analysis of hprt mutations induced by estradiol in Chinese hamster V79 cells.

L. Y. Kong, P. Szaniszlo, T. Albrecht, J. G. Liehr

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The natural hormone estradiol (E2) 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 E2 has led us to re-examine the mutation frequency and molecular alterations of the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene in Chinese hamster V79 cells. E2 at both physiological and pharmacological concentrations (10-11, 10-10, and 10-7, 10-6 M) significantly increased the mutation frequency of the hprt gene by 2. 57-, 3.45-, 2.63-, and 8.78-fold, respectively, compared to the controls, while 10-13, 10-12, 10-9, or 10-8 M E2 induced little change (<or =0.93-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 picked E2-induced mutants (71%). Simple base substitutions, such as Tright curved arrow G or Tright curved arrow 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 Aright curved arrow G and a Cright curved arrow 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 (ERalpha). However, ICI 182,780, an antagonist of ERalpha, acted in an additive manner with E2 and increased the hprt mutation frequency. In conclusion, E2 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 E2 in V79 cells are not mediated by the ERalpha.

Original languageEnglish (US)
Pages (from-to)1141-1149
Number of pages9
JournalInternational Journal of Oncology
Volume17
Issue number6
StatePublished - Dec 2000
Externally publishedYes

Fingerprint

Hypoxanthine Phosphoribosyltransferase
Cricetulus
Estradiol
Mutation Rate
Estrogen Receptor alpha
Mutation
Sequence Deletion
Clone Cells
Hormones
Polymerase Chain Reaction
Point Mutation
Genes
DNA Damage
Rodentia
Complementary DNA
Pharmacology
DNA
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Frequency and molecular analysis of hprt mutations induced by estradiol in Chinese hamster V79 cells. / Kong, L. Y.; Szaniszlo, P.; Albrecht, T.; Liehr, J. G.

In: International Journal of Oncology, Vol. 17, No. 6, 12.2000, p. 1141-1149.

Research output: Contribution to journalArticle

Kong, LY, Szaniszlo, P, Albrecht, T & Liehr, JG 2000, 'Frequency and molecular analysis of hprt mutations induced by estradiol in Chinese hamster V79 cells.', International Journal of Oncology, vol. 17, no. 6, pp. 1141-1149.
Kong, L. Y. ; Szaniszlo, P. ; Albrecht, T. ; Liehr, J. G. / Frequency and molecular analysis of hprt mutations induced by estradiol in Chinese hamster V79 cells. In: International Journal of Oncology. 2000 ; Vol. 17, No. 6. pp. 1141-1149.
@article{3a43eda03fab4b51b8923c2113f2b9ed,
title = "Frequency and molecular analysis of hprt mutations induced by estradiol in Chinese hamster V79 cells.",
abstract = "The natural hormone estradiol (E2) 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 E2 has led us to re-examine the mutation frequency and molecular alterations of the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene in Chinese hamster V79 cells. E2 at both physiological and pharmacological concentrations (10-11, 10-10, and 10-7, 10-6 M) significantly increased the mutation frequency of the hprt gene by 2. 57-, 3.45-, 2.63-, and 8.78-fold, respectively, compared to the controls, while 10-13, 10-12, 10-9, or 10-8 M E2 induced little change (",
author = "Kong, {L. Y.} and P. Szaniszlo and T. Albrecht and Liehr, {J. G.}",
year = "2000",
month = "12",
language = "English (US)",
volume = "17",
pages = "1141--1149",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "6",

}

TY - JOUR

T1 - Frequency and molecular analysis of hprt mutations induced by estradiol in Chinese hamster V79 cells.

AU - Kong, L. Y.

AU - Szaniszlo, P.

AU - Albrecht, T.

AU - Liehr, J. G.

PY - 2000/12

Y1 - 2000/12

N2 - The natural hormone estradiol (E2) 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 E2 has led us to re-examine the mutation frequency and molecular alterations of the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene in Chinese hamster V79 cells. E2 at both physiological and pharmacological concentrations (10-11, 10-10, and 10-7, 10-6 M) significantly increased the mutation frequency of the hprt gene by 2. 57-, 3.45-, 2.63-, and 8.78-fold, respectively, compared to the controls, while 10-13, 10-12, 10-9, or 10-8 M E2 induced little change (

AB - The natural hormone estradiol (E2) 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 E2 has led us to re-examine the mutation frequency and molecular alterations of the hypoxanthine-guanine phosphoribosyltransferase (hprt) gene in Chinese hamster V79 cells. E2 at both physiological and pharmacological concentrations (10-11, 10-10, and 10-7, 10-6 M) significantly increased the mutation frequency of the hprt gene by 2. 57-, 3.45-, 2.63-, and 8.78-fold, respectively, compared to the controls, while 10-13, 10-12, 10-9, or 10-8 M E2 induced little change (

UR - http://www.scopus.com/inward/record.url?scp=0034547177&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034547177&partnerID=8YFLogxK

M3 - Article

C2 - 11078799

AN - SCOPUS:0034547177

VL - 17

SP - 1141

EP - 1149

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 6

ER -