Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2000 Feb 14;447(2):257-65.
doi: 10.1016/s0027-5107(99)00220-1.

Toxicity, mutation frequency and mutation spectrum induced by dacarbazine in CHO cells expressing different levels of O(6)-methylguanine-DNA methyltransferase

Affiliations

Toxicity, mutation frequency and mutation spectrum induced by dacarbazine in CHO cells expressing different levels of O(6)-methylguanine-DNA methyltransferase

M C Psaroudi et al. Mutat Res. .

Abstract

The toxicity and mutagenicity (including the mutation spectrum induced) of dacarbazine, a methylating cytostatic drug, was examined in CHO cells expressing different levels of the repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT). Expression of low or high levels of a transfected human MGMT gene under the control of the metallothionein promoter protected the cells against dacarbazine-induced toxicity and mutagenesis. In the absence of MGMT expression, the mutation spectrum in the HPRT locus was dominated by GC-->AT transitions (mostly found at 5'Pu-G sequences), while there were also a few AT-->GC transitions. Expression MGMT was associated with a substantial decrease of GC-->AT mutations, suggesting that these mutations arose primarily via O(6)-methylguanine. These data illustrate the important role of the latter lesion in the drug's mutagenic and cytotoxic activity.

PubMed Disclaimer

Publication types

MeSH terms

LinkOut - more resources