Analysis of alkylating mutagenesis in CHO cells

Conference · Sat Jan 01 04:00:00 EST 1983

OSTI ID:6353014

Hsie, A W; Stankowski, Jr, L F; Schenley, R L; Foote, R S; Mitra, S; Thielmann, H W

The CHO/HGPRT assay was used to quantify cytotoxicity and mutation at the HGPRT locus induced by various chemicals to study structure-mutagenicity relationships. On an equimolar basis within each structurally related group (nitrosamidines, nitrosamides, alkyl alkanesulfonates and alkylsulfates), chemical reactivity with DNA (s value), mutagenicity and cytotoxicity decrease with increasing size of the alkyl group, with the methyl agents being more mutagenic and cytotoxic than the corresponding ethylating agents. However, significantly different relationships are observed if comparisons are made at equitoxic levels. The possible role of alkylated dNTPs, produced within cells by treatment with simple slkylating agents, in mutagenesis was studied. Using a modified treatment protocol, individual dNTP adducts can be introduced into CHO cells at significant levels. m/sup 6/dGTP was found to be neither cytotoxic nor mutagenic. Experiments using (8-/sup 3/H)m/sup 6/dGTP indicate that this alkylated dNTP, as it occurs in the intact cell, is not a precursor for DNA synthesis. Instead, it appears that this analog can be interconverted to other nucleoside and nucleotide forms, one of which (0/sup 6/-methyldeoxyguanosine) can be repaired by adenosine deaminase. This modified treatment protocol seems to hold promise for the study of other dNTP adducts, as well as other highly charged, usually-nonpermeable molecules. 26 references, 5 tables.

• Research Organization: Oak Ridge National Lab., TN (USA); Tennessee Univ., Oak Ridge (USA). Graduate School of Biomedical Sciences; Deutsches Krebsforschungszentrum, Heidelberg (Germany, F.R.). Inst. fuer Biochemie
• DOE Contract Number: AC05-84OR21400
• OSTI ID: 6353014
• Report Number(s): CONF-831291-1; ON: DE85001556
• Country of Publication: United States
• Language: English

Related Subjects

560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
ANIMAL CELLS
CELL CULTURES
CHO CELLS
CORRELATIONS
DATA
EXPERIMENTAL DATA
INFORMATION
METABOLITES
MOLECULAR STRUCTURE
MUTAGEN SCREENING
NUMERICAL DATA
SCREENING
TOXICITY