Analysis of DNA adducts in human samples: Acrolein‐derived exocyclic DNA adducts as an example

Abstract

Acrolein is an environmental pollutant that is also derived endogenously through lipid peroxidation and protein degradation. The reaction of acrolein with 2'-deoxyguanosine produces exocyclic 1,N(2) -propano-2'-deoxyguanosine (AdG) adducts, mutagenic lesions that play important roles in multistage carcinogenesis processes. Accurate quantification of acrolein-derived DNA adducts is a critical step toward elucidating the mode of action of acrolein carcinogenicity. Exposure of humans to acrolein can occur through the smoking of tobacco and the dietary consumption of oxidized polyunsaturated fatty acids. This review describes the use of (32) P-postlabeling- and MS-based methods for the analyses of acrolein-derived DNA adducts in humans as well as present trends toward improving the sensitivity, specificity, and accuracy of the quantification of trace amounts of DNA adducts in DNA of limited availability.

Occurrence, Biological Consequences, and Human Health Relevance of Oxidative Stress-Induced DNA Damage

“…For instance, the use of small internal diameter columns coupled with nLC-nESI-MS systems has already facilitated the quantitative analysis of multiple oxidatively induced DNA lesions with the use of low microgram quantity of DNA. 88,159,160,163,165 Recently, high-resolution Orbitrap mass spectrometers have been used for the detection of alkylated DNA lesions induced by carcinogens present in tobacco smoke. 344,345 Owing to their accurate mass measurement capability and high sensitivity, we expect more applications of this type of instruments for the quantification of low levels of oxidatively generated DNA lesions in cellular and tissue samples in the future.…”

DNA and protein adducts in human tissues resulting from exposure to tobacco smoke

“…It reacts with DNA to form primarily N 2 ‐ethylidene‐dGuo, which when DNA is subjected to enzyme hydrolysis in the presence of NaBH 3 CN is converted to N 2 ‐ethyl‐dGuo, detectable by LC‐ESI‐MS/MS‐SRM 37 . N 2 ‐ethyl‐dGuo was detected thus in the blood leukocyte DNA of 25 smokers at levels of 1,310 ± 720 (range: 124–7,700) and 1,120 ± 1,140 (range: 138–5,760) fmol/μmol dGuo at two baseline points 94…”

“…There is inadequate evidence for its human carcinogenicity 93. Chen94 has reviewed the use of 32 P‐postlabelling‐ and MS‐based methods for the analyses of acrolein‐derived DNA adducts in human tissues.…”

“…37 N 2ethyl-dGuo was detected thus in the blood leukocyte DNA of 25 smokers at levels of 1,310 6 720 (range: 124-7,700) and 1,120 6 1,140 (range: 138-5,760) fmol/lmol dGuo at two baseline points. 94 Theoretically, subsequent reaction of N 2 -ethylidene-dGuo in DNA would give rise to 1,N 2 -propano-dGuo (1,N 2 -edGuo, i.e., Acr-dGuo). This adduct has been detected in human cells exposed in vitro to micromolar concentrations of acetaldehyde.…”

Inflammation and Pyroptosis Mediate Muscle Expansion in an Interleukin-1β (IL-1β)-dependent Manner

“…CPX is a chemotherapeutic agent that metabolizes to acrolein and accumulates in the bladder of patients (10 -14). Mesna is administered to patients given CPX in order to sequester the acrolein to limit inflammatory bladder complications (15 Acrolein is a naturally occurring mutagenic breakdown product of both carbohydrates and lipids (associated with high temperature cooking); however, acrolein exposure through cigarette smoking is the largest proportion of human exposure (16). There are multiple reports of CPX-induced urinary bladder cystitis associated with an increase in voiding frequency and a decrease in urine volume per void (11,17,18).…”