Methylnitronitrosoguanidine (MNNG) is an orally active alkylating agent, shows toxic and mutagenic effects. Methylnitronitrosoguanidine often used as carcinogen and mutagen in vivo and in vitro [1,2]. The MNNG mechanism of action is owing to its electrophilic compound degradations, where ammonium ion is the mutagen and leads to the electrophilic impact on DNA base pairs specifically on its nucleophilic sites [3].
After Methylnitronitrosoguanidine (3 µg/mL) treatment, the ultrastructure of the OC3W3-15 cells possessed larger nuclei with enlarged and prominent nucleoli, usually more than 2 in number. The amount of heterochromatin decreased while euchromatin increased. The cytoplasm was filled with abundant rough endoplasmic reticulum, free ribosomes, Golgi apparatus, and well-developed mitochondria, yet the nuclear-to-cytoplasmic ratio remained high [2]. Methylnitronitrosoguanidine (3 µg/mL) treatment increased proliferative rate of hepatic oval cells, and more cells were in prophase for rapid proliferation than in the control group [2]. 2×10-4 mol/L Methylnitronitrosoguanidine could increase the proliferation, promote the invasion and migration, suppress the apoptosis of GES-1 cells. The expression levels of NF-κB p65 mRNA and protein were upregulated in GES-1 cells after treatment with MNNG [4].
Methylnitronitrosoguanidine (200 mg/kg, 2 weeks) treatment significantly decreased the Male Wistar albino rats body weights, increased tumor weight and gastric cancer was induced in 100% of the rats [1]. Methylnitronitrosoguanidine (200 mg/kg, 2 weeks) reduced protein levels of Bax, caspase-3, and -9 [1].
References:
[1]. Zhang L, Jia B, Velu P, et al. Corilagin induces apoptosis and inhibits HMBG1/PI3K/AKT signaling pathways in a rat model of gastric carcinogenesis induced by methylnitronitrosoguanidine[J]. Environmental Toxicology, 2022, 37(5): 1222-1230.
[2]. Ding L, Ding Y N, Lin Y, et al. Proteins related to early changes in carcinogenesis of hepatic oval cells after treatment with methylnitronitrosoguanidine[J]. Experimental and Toxicologic Pathology, 2014, 66(2-3): 139-146.
[3]. Zhu, F., Xu, Y., Pan, J., Li, M., Chen, F., & Xie, G. (2021). Epigallocatechin gallate protects against MNNG-induced precancerous lesions of gastric carcinoma in rats via PI3K/Akt/mTOR pathway. Evidence-Based Complementary and Alternative Medicine, 2021.
[4]. XU J, ZHANG X, SUN D, et al. Effect of methylnitronitrosoguanidine (MNNG) on the malignant transformation of human gastric mucosa GES-1 cells and its mechanism[J]. Medical Journal of Chinese People's Liberation Army, 2016, 41(11): 887-891.
甲基亚硝基胍 (MNNG) 是一种具有口服活性的烷化剂,具有毒性和致突变作用。甲基亚硝基胍常被用作体内外致癌物和诱变剂[1,2]。 MNNG 的作用机制是由于其亲电化合物降解,其中铵离子是诱变剂,导致对 DNA 碱基对的亲电影响,特别是在其亲核位点 [3]。
在甲基亚硝基胍 (3 µg/mL) 处理后,OC3W3-15 细胞的超微结构具有较大的细胞核,核仁增大且突出,通常数量超过 2 个。异染色质减少而常染色质增加。细胞质中充满了丰富的粗面内质网、游离核糖体、高尔基体和发育良好的线粒体,但核质比仍然很高[2]。甲基亚硝基胍(3 µg/mL)处理提高了肝卵圆细胞的增殖率,并且比对照组有更多的细胞处于快速增殖的前期[2]。 2×104 mol/L Methylnitronitrosoguanidine可促进GES-1细胞增殖,促进侵袭和迁移,抑制细胞凋亡。 MNNG[4]处理后GES-1细胞NF-κB p65 mRNA和蛋白表达上调。
甲基亚硝基胍（200 mg/kg, 2周)治疗显着降低了雄性 Wistar 白化大鼠的体重,增加了肿瘤重量,并且在 100% 的大鼠中诱发了胃癌 [1]。甲基亚硝基胍（200 mg/kg,2 周）降低 Bax、caspase-3 和 -9 的蛋白质水平[1]。