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An in vitro study on the interaction between dimethylnitrosamine and nucleic acids via a microsomal system
Gan
|April 1, 1977
Summary
Dimethylnitrosamine (DMNA) incubation in a microsomal system did not yield radioactive alkylated bases in DNA or RNA. Instead, two novel radioactive compounds were detected, challenging the established N-7 guanine alkylation mechanism.
Area of Science:
- Biochemistry
- Molecular Biology
- Toxicology
Background:
- Dimethylnitrosamine (DMNA) is a known carcinogen.
- The generally-accepted mechanism involves alkylation at the N-7 position of guanine in DNA.
Purpose of the Study:
- To investigate the in vitro alkylation products of DMNA in a microsomal system.
- To determine if radioactive alkylated bases are formed from DMNA in nucleic acids.
Main Methods:
- Incubation of polyribonucleotides and DNA with 14C-dimethylnitrosamine (DMNA) in a microsomal system.
- Acid and alkaline hydrolysis of nucleic acids.
- Chromatographic analysis (column, paper, and thin-layer) of hydrolysates.
Main Results:
- No radioactive alkylated bases, ribose, or phosphate were detected in nucleic acid hydrolysates.
- Two consistent radioactive compounds were observed, co-chromatographing with methylamine and N-methylhydrazine.
- These compounds differed from the product of alkali-mediated imidazole ring fission of 7-methylguanosine.
Conclusions:
- The in vitro system accurately reflects in vivo conditions for DMNA metabolism.
- The results contradict the widely accepted N-7 guanine alkylation mechanism for DMNA.
- Novel pathways or products may be involved in DMNA-induced DNA damage.