4-Nitroquinoline-1-oxide-induced mutagen sensitivity and risk of cutaneous melanoma

Abstract

Mutagen sensitivity assay, which measures the enhanced cellular response to DNA damage induced in vitro by mutagens/carcinogens, has been used in the study of cancer susceptibility. 4-Nitroquinoline-1-oxide (4-NQO), an ultraviolet (UV) radiation-mimetic chemical, can produce chromosomal breaks in mammalian cells and induce cancer. Given the potential role of 4-NQO as the experimental mutagen substituting for UV as the etiological carcinogen of cutaneous melanoma (CM), we tested the hypothesis that cellular sensitivity to 4-NQO is associated with the risk of developing CM in a case–control study of 133 patients with primary CM and 176 cancer-free controls. Short-term blood cultures were treated with 4-NQO at a final concentration of 10 µmol/l for 24 h and scored chromatid breaks in 50 well-spread metaphases. Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals. We found that the log-transformed frequency of chromatid breaks was significantly higher in 133 patients than in 176 controls (P = 0.004) and was associated with an increased risk for CM (adjusted odds ratio = 1.78, 95% confidence interval: 1.12–2.84) after adjustment for age and sex. Moreover, as the chromatid break values increased, the risk for CM increased in a dose-dependent manner (Ptrend = 0.003). Further analysis explored a multiplicative interaction between the sensitivity to 4-NQO and a family history of skin cancer (Pinteraction = 0.004) on the risk of CM. Therefore, our findings suggest that sensitivity to 4-NQO may be a risk factor for the risk of CM, which is more sensitive than UV-induced chromosome breaks.

Porphyromonas gingivalis Promotes 4-Nitroquinoline-1-Oxide-Induced Oral Carcinogenesis With an Alteration of Fatty Acid Metabolism

“…To elucidate the role of P. gingivalis in OSCC development, a combined experimental system of 4NQO-induced oral carcinoma model and P. gingivalis- induced chronic periodontitis model was established as described previously ( Binder Gallimidi et al, 2015 ; Wang et al, 2016 ). The consumption of water and basal diet per mouse of each group was comparable.…”

ADH2/GSNOR1 is a key player in limiting genotoxic damage mediated by formaldehyde and UV‐B in Arabidopsis

“…The UV radiation-mimetic chemical 4-nitroquinoline-1-oxide (4NQO) has been shown to mimic the biological effects of ultraviolet light on various organisms (Ikenaga et al, 1975;Wang et al, 2016). 4NQO, as a DNA damage agent, induces bulky lesions (Wang et al, 2011).…”

Hybrid adaptation is hampered by Haldane’s sieve

“…Some environmental conditions and stresses could further enhance genome instability, so what appears as a feature that enhances adaptability in benign conditions could become a liability in extreme ones. Motivated by this question, in a previous study 49 , we produced F1 hybrids between the budding yeast Saccharomyces cerevisiae and S. paradoxus to measure their adaptive potential in an environment containing a drug that increases genomic instability by mimicking UV radiation 50,51 . These two species diverged 5-10 million years ago [52][53][54][55][56] , live in similar ecological niches in nature 57 , and carry signs for introgression in their mitochondrial and nuclear genomes with adaptive potential in some cases 47,[58][59][60][61] .…”