Journal Article

The influence of cellular apoptotic capacity on N-nitrosodimethylamine-induced loss of heterozygosity mutations in human cells.

K L Dobo, D A Eastmond and A J Grosovsky

in Carcinogenesis

Volume 18, issue 9, pages 1701-1707
Published in print January 1997 | ISSN: 0143-3334
Published online January 1997 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/18.9.1701
The influence of cellular apoptotic capacity on N-nitrosodimethylamine-induced loss of heterozygosity mutations in human cells.

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

The induction of loss of heterozygosity (LOH) by the environmental carcinogen N-nitrosodimethylamine (NDMA), and the factors that influence the recovery of LOH mutations were studied in two directly related human lymphoblastoid cell lines, AHH-1 (h2E1.v2) and MCL-5. Initially, the NDMA-induced mutation frequency at the heterozygous tk locus in AHH-1 cells was observed to be 5-fold higher in AHH-1 compared with MCL-5. Molecular analysis of NDMA-induced TK- mutants indicated that the induced mutant fraction attributable to small intragenic mutations was similar in both cell lines. However, the induced mutant fraction, because of LOH, was 18-fold greater in AHH-1. In addition, LOH mutations were more extensive among TK- mutants derived from AHH-1 cells. We hypothesized that the increased recovery of large LOH mutations in AHH-1 cells could be attributable to reduced apoptotic capacity, as it has been reported that AHH-1 cells carry a heterozygous mutation in the p53 locus, whereas MCL-5 cells are homozygous wild-type. Analysis of the kinetics of apoptosis showed that the apoptotic response of the AHH-1 cell line was diminished and delayed compared with MCL-5. Based on the analyses presented here, and several recent reports, it is suggested that the recovery of LOH mutations in p53 deficient cell lines is affected not only by abnormalities in cellular apoptotic response, but also involves a number of p53-mediated responses to DNA damage.

Journal Article.  0 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.