Methylnitronitrosoguanidine(wetted with ca. 50% Water)

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]. 2×104 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.