Inhibition of Uracil DNA Glycosylase Alters Frequency and Spectrum of Action-at-a-Distance Mutations Induced by 8-Oxo-7,8-dihydroguanine.

The generation of DNA damage causes mutations and consequently cancer. Reactive oxygen species are important sources of DNA damage and some mutation signatures found in human cancers. 8-Oxo-7,8-dihydroguanine (G, 8-hydroxyguanine) is one of the most abundant oxidized bases and induces a G→T transversion mutation at the modified site.

Recombinant hepatocyte growth factor accelerates cutaneous wound healing in a diabetic mouse model.

We examined effects of recombinant hepatocyte growth factor (HGF) on cutaneous wound healing, using a full-thickness cutaneous excision model in diabetic mice. Topical administration of HGF, as well as basic fibroblast growth factor (bFGF), promoted the rate of wound closure and re-epithelialization. Both HGF and bFGF enhanced expansion of the granulation tissue and stimulated neovascularization on day 7 postwounding, wherein the increase in microvessel density in HGF-treated wounds was higher than that in bFGF-treated wounds.

Neutralization of hepatocyte growth factor leads to retarded cutaneous wound healing associated with decreased neovascularization and granulation tissue formation.

To elucidate biologic functions of hepatocyte growth factor and the c-Met receptor in cutaneous wound healing, we analyzed expression and localization of hepatocyte growth factor and c-Met receptor and used a strategy to neutralize endogenous hepatocyte growth factor in a cutaneous wound healing model in mice. Following excision of full-thickness skin on the dorsum of mice, expression of both hepatocyte growth factor and the c-Met receptor increased transiently in cutaneous tissues. Expressions of hepatocyte growth factor increased as early as 2 d postwounding and reached a peak on day 2, whereas the c-Met receptor expression reached a peak 2-4 d postwounding.