Adriamycin induces large deletions as a major type of mutation in CHO cells

Yongjia Yu, Zhidong Xu, Abraham W. Hsie

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Adriamycin (ADR), a commonly used cancer chemotherapy antibiotic, exhibits a variety of genotoxicities. In this study, we have examined the mutagenicity of ADR at the hypoxanthine-guanine phosphoribosyltransferase gene (hprt) in Chinese hamster ovary (CHO) cells and the xanthine-guanine phosphoribosyltransferase locus (gpt) in a pSV2gpt-transformed CHO cell line, AS52. Although ADR induced a dose-dependent increase of mutant frequency at both loci, it was more mutagenic to the gpt gene than to the hprt locus. Multiplex PCR analysis revealed that 35% of the 103 independent ADR-induced HPRT-deficient mutants carried large deletions. Among these deletion mutants, 33% were total gene deletions, 22% affected multiple exons, and 42% involved a single exon, of which most (9/15) were exon 1. The majority (63%) of ADR-induced AS52 mutants had a total deletion of the gpt gene. These observations indicate that ADR induces large deletions as a major type of gene mutation in mammalian cells, suggesting the involvement of reactive oxygen species as one mutagenic pathway in the mutagenesis of ADR.

Original languageEnglish (US)
Pages (from-to)91-98
Number of pages8
JournalMutation Research Letters
Volume325
Issue number2-3
DOIs
StatePublished - 1994

Fingerprint

Cricetulus
Doxorubicin
Hypoxanthine Phosphoribosyltransferase
Ovary
Genes
Mutation
Exons
Cells
Mutagenesis
Chemotherapy
Multiplex Polymerase Chain Reaction
Gene Deletion
Reactive Oxygen Species
Anti-Bacterial Agents
Drug Therapy
Cell Line
Neoplasms

Keywords

  • Adriamycin
  • Chinese hamster cells
  • Deletion
  • gpt
  • hprt
  • Multiplex PCR

ASJC Scopus subject areas

  • Genetics
  • Toxicology

Cite this

Adriamycin induces large deletions as a major type of mutation in CHO cells. / Yu, Yongjia; Xu, Zhidong; Hsie, Abraham W.

In: Mutation Research Letters, Vol. 325, No. 2-3, 1994, p. 91-98.

Research output: Contribution to journalArticle

Yu, Yongjia ; Xu, Zhidong ; Hsie, Abraham W. / Adriamycin induces large deletions as a major type of mutation in CHO cells. In: Mutation Research Letters. 1994 ; Vol. 325, No. 2-3. pp. 91-98.
@article{dee367428692417b906ad9e5cce563fe,
title = "Adriamycin induces large deletions as a major type of mutation in CHO cells",
abstract = "Adriamycin (ADR), a commonly used cancer chemotherapy antibiotic, exhibits a variety of genotoxicities. In this study, we have examined the mutagenicity of ADR at the hypoxanthine-guanine phosphoribosyltransferase gene (hprt) in Chinese hamster ovary (CHO) cells and the xanthine-guanine phosphoribosyltransferase locus (gpt) in a pSV2gpt-transformed CHO cell line, AS52. Although ADR induced a dose-dependent increase of mutant frequency at both loci, it was more mutagenic to the gpt gene than to the hprt locus. Multiplex PCR analysis revealed that 35{\%} of the 103 independent ADR-induced HPRT-deficient mutants carried large deletions. Among these deletion mutants, 33{\%} were total gene deletions, 22{\%} affected multiple exons, and 42{\%} involved a single exon, of which most (9/15) were exon 1. The majority (63{\%}) of ADR-induced AS52 mutants had a total deletion of the gpt gene. These observations indicate that ADR induces large deletions as a major type of gene mutation in mammalian cells, suggesting the involvement of reactive oxygen species as one mutagenic pathway in the mutagenesis of ADR.",
keywords = "Adriamycin, Chinese hamster cells, Deletion, gpt, hprt, Multiplex PCR",
author = "Yongjia Yu and Zhidong Xu and Hsie, {Abraham W.}",
year = "1994",
doi = "10.1016/0165-7992(94)90007-8",
language = "English (US)",
volume = "325",
pages = "91--98",
journal = "Mutation Research Letters",
issn = "0165-7992",
publisher = "Elsevier BV",
number = "2-3",

}

TY - JOUR

T1 - Adriamycin induces large deletions as a major type of mutation in CHO cells

AU - Yu, Yongjia

AU - Xu, Zhidong

AU - Hsie, Abraham W.

PY - 1994

Y1 - 1994

N2 - Adriamycin (ADR), a commonly used cancer chemotherapy antibiotic, exhibits a variety of genotoxicities. In this study, we have examined the mutagenicity of ADR at the hypoxanthine-guanine phosphoribosyltransferase gene (hprt) in Chinese hamster ovary (CHO) cells and the xanthine-guanine phosphoribosyltransferase locus (gpt) in a pSV2gpt-transformed CHO cell line, AS52. Although ADR induced a dose-dependent increase of mutant frequency at both loci, it was more mutagenic to the gpt gene than to the hprt locus. Multiplex PCR analysis revealed that 35% of the 103 independent ADR-induced HPRT-deficient mutants carried large deletions. Among these deletion mutants, 33% were total gene deletions, 22% affected multiple exons, and 42% involved a single exon, of which most (9/15) were exon 1. The majority (63%) of ADR-induced AS52 mutants had a total deletion of the gpt gene. These observations indicate that ADR induces large deletions as a major type of gene mutation in mammalian cells, suggesting the involvement of reactive oxygen species as one mutagenic pathway in the mutagenesis of ADR.

AB - Adriamycin (ADR), a commonly used cancer chemotherapy antibiotic, exhibits a variety of genotoxicities. In this study, we have examined the mutagenicity of ADR at the hypoxanthine-guanine phosphoribosyltransferase gene (hprt) in Chinese hamster ovary (CHO) cells and the xanthine-guanine phosphoribosyltransferase locus (gpt) in a pSV2gpt-transformed CHO cell line, AS52. Although ADR induced a dose-dependent increase of mutant frequency at both loci, it was more mutagenic to the gpt gene than to the hprt locus. Multiplex PCR analysis revealed that 35% of the 103 independent ADR-induced HPRT-deficient mutants carried large deletions. Among these deletion mutants, 33% were total gene deletions, 22% affected multiple exons, and 42% involved a single exon, of which most (9/15) were exon 1. The majority (63%) of ADR-induced AS52 mutants had a total deletion of the gpt gene. These observations indicate that ADR induces large deletions as a major type of gene mutation in mammalian cells, suggesting the involvement of reactive oxygen species as one mutagenic pathway in the mutagenesis of ADR.

KW - Adriamycin

KW - Chinese hamster cells

KW - Deletion

KW - gpt

KW - hprt

KW - Multiplex PCR

UR - http://www.scopus.com/inward/record.url?scp=0028173303&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028173303&partnerID=8YFLogxK

U2 - 10.1016/0165-7992(94)90007-8

DO - 10.1016/0165-7992(94)90007-8

M3 - Article

C2 - 7523937

AN - SCOPUS:0028173303

VL - 325

SP - 91

EP - 98

JO - Mutation Research Letters

JF - Mutation Research Letters

SN - 0165-7992

IS - 2-3

ER -