A warning about NAC for those who have emphysema or COPD. https://t.co/dyEiCxmWVJ
— DCGreenZone1 (@DCGreenZone) July 6, 2022
Lung adenocarcinoma development in NAC-treated mice.
Lung tissue histology in aged NAC-treated animals revealed the formation of tumors exhibiting lung adenocarcinoma characteristics in 50% of JunD–/– mice and in 10% of controls (Figure 4, A and B). The appearance of the tumors was typical of adenocarcinoma with conspicuous papillary structures associated with a collagen network that stained with Sirius Red, as reported in previous studies (Figure 4, C and D, and ref. 15). Adenocarcinoma tissue sections were also characterized by high counts of Ki67-positive cells compared with nonadenocarcinoma tissue (Figure 4E). In contrast, p21 and p16 staining activities were not detected in adenocarcinoma tissue (Figure 4F). No such tumors were detected in vehicle-treated JunD–/– or control mice, even when studied until 24 months of age. No animals in any group had tumors detected in the liver, spleen, or kidneys. Moreover, in situ studies detected no associated lesions in mice with lung cancer. Inflammatory infiltrates were detected in the lungs of most of the aged mice (Figure 4G) and were more marked in the aged JunD–/– mice than in their controls but were not affected by NAC treatment (Figure 4G). These changes were not related to alterations in lung levels of mucin (16), which did not differ between aged and young mice and which was not affected by JunD inactivation (Supplemental Figure 2).
Definitely interesting and well-worth a conscious pause in the use of NAC. Other antioxidants are available that seemingly have no increased risk of tumor growth.
Cell senescence is known to inhibit cell transformation and tumor initiation. We consequently hypothesized that NAC treatment promoted tumor initiation by inducing escape from cell senescence (17, 18). Interestingly, p16- and p21-stained cells, although sparsely distributed in lungs from NAC-treated mice, were not seen within tumors (Figure 4F). In contrast, Ki67-stained cells were seen only within tumors (Figure 4B). JunD–/–-derived mouse embryonic fibroblasts (MEFs) display p53-dependent premature senescence (19), and NAC treatment decreases p53 levels in the context of lung tumor progression in mice (8). Accordingly, we found decreased lung p53 protein and p16 mRNA levels in NAC-treated aged mice (Supplemental Figures 3 and 4), supporting the concept that NAC limits the expression of key senescence effectors and tumor suppressor genes
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