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Reduction of nicotinamide adenine dinucleotide levels by ultimate carcinogens in human lymphocytes
Abstract:
The effect of several classes of DNA-damaging chemicals and closely related compounds on cellular nicotinamide adenine dinucleotide (NAD) levels was studied in freshly isolated peripheral human lymphocytes. Of the 21 compounds examined, 7 were direct DNA-damaging agents and 14 were non-DNA-damaging compounds or required metabolic activation to casue DNA damage. Rapid lowering of cellular NAD levels was caused by each of the direct DNA-damaging chemicals examined in this study including N-methyl-N'-nitr-N-nitrosoguanidine, methyl methanesulfonate, N-acetoxy-2-acetylaminofluorene, 7-bromomethylbenz(a)anthracene, and the benzo(a)pyrene derivatives, r-7,t-8-dihydroxy-9, 10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene and benzo(a)pyrene-4,5-epoxide. The indirect-acting carcinogen 2-acetylaminofluorene, 13 polycyclic aromatic hydrocarbons, and derivatives that were non-DNA-damaging did not cause lowering of NAD. The results suggest a general correlation between DNA damage and acute lowering of cellular NAD pools.
Insights
Directly DNA-damaging chemicals rapidly lower cellular nicotinamide adenine dinucleotide (NAD) levels in human lymphocytes. Non-DNA-damaging compounds did not affect NAD, suggesting a link between DNA damage and NAD depletion.
Area of Science:
- Biochemistry
- Toxicology
- Molecular Biology
Background:
- Cellular nicotinamide adenine dinucleotide (NAD) is crucial for various biological processes.
- DNA-damaging chemicals can disrupt cellular homeostasis.
- Understanding the relationship between DNA damage and NAD levels is important for toxicology and disease research.
Purpose of the Study:
- To investigate the impact of various DNA-damaging and non-DNA-damaging chemicals on cellular NAD levels in human lymphocytes.
- To determine if a correlation exists between direct DNA damage and the depletion of NAD pools.
Main Methods:
- Freshly isolated peripheral human lymphocytes were exposed to 21 different chemical compounds.
- Compounds were classified as direct DNA-damaging agents or non-DNA-damaging agents.
- Cellular NAD levels were measured following exposure to these chemicals.
Main Results:
- Directly DNA-damaging chemicals, including N-methyl-N'-nitr-N-nitrosoguanidine and benzo(a)pyrene derivatives, caused a rapid decrease in cellular NAD levels.
- Non-DNA-damaging compounds, such as 2-acetylaminofluorene and polycyclic aromatic hydrocarbons, did not significantly alter NAD levels.
- A clear correlation was observed between the direct DNA-damaging potential of chemicals and the acute lowering of cellular NAD.
Conclusions:
- Direct DNA damage is strongly associated with a rapid reduction in cellular NAD pools.
- This finding suggests a potential biomarker role for NAD levels in response to genotoxic agents.
- Further research can explore the mechanisms linking DNA damage and NAD depletion.