Diethylnitrosamine den

Oridonin was obtained from the Shaanxi Huike Botanical Development Co., Ltd., Shaanxi, China. Poly(lactic-co-glycolic)acid (PLGA, lactide/glycolide, 50:50, mol/mol, MW 10 kDa) was produced by Jinan Daigang Biomaterial Co., Ltd., Shandong, China. Gemcitabine, used as a positive control drug, was purchased from Hansoh Pharmaceutical Co., Ltd., Jiangsu, China. Polyvinyl alcohol (PVA, 87%–89% alcoholysis, MW 75000 Da) was purchased from the Aladdin Industrial Corporation, Shanghai, China, and ammonium bicarbonate was purchased from the Sinopharm Chemical Reagent Co., Ltd., Beijing, China. Cy7 was purchased from Fanbo Biochemicals Co., Ltd., Beijing, China. 3-Methyl cholanthrene (MCA, Sigma, USA), diethyl nitrosamine (DEN, Tokyo Chemical Industry, Japan), and iodized oil (Guerbet, French) were used. Anti-BCL-2 and anti-BAX antibodies were from the Cell Signaling Technology Inc. (Danvers, USA). All other chemicals and solvents were of analytical grade or high performance liquid chromatographic (HPLC) grade.

Resorufin, ethoxyResorufin and pentoxyResorufin were purchased from Sigma-Aldrich Inc. (St. Louis, MO, U.S.A.). Tolbutamide, hydroxyl- tolbutamide, midazolam, 4-hydroxymidazolam, bufuralol and 1’-hydroxybufuralol were purchased
from Daiichi Chemical (Tokyo, Japan). Aniline and p-aminophenol were obtained from Wako Pure Chemical (Osaka, Japan). All the other chemicals were of analytical or HPLC grade.
Diethylnitrosamine (DEN) was purchased from Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan). Prior to administration, DEN was dissolved in physiological saline (Otsuka Pharmaceutical Factory, Inc., Tokushima, Japan) and
administered by oral gavage. The dose for DEN was selected based on data that showed positive results in the juvenile rat liver MN assay [29 (link),30 (link),31 (link),32 (link),33 (link)]. Negative control animals received physiological saline (DEN solvent).

Curcumin was provided by Sinopharm Reagent Co., Ltd. (Shanghai, China). Soybean lecithin (SPC>90%) and cholesterol were purchased from Shanghai Taiwei Medicine Co., Ltd. (China) and Sinopharm Reagent Co., Ltd. (Shanghai, China), respectively. Gemcitabine was provided by Jiangsu Hansoh Pharmaceutical Co., Ltd., China. 3-Methylcholanthrene (MCA, TRC, USA), diethylnitrosamine (DEN, Tokyo Chemical Industry, Japan) and iodized oil (Guerbet, French) were used for generating rat primary lung cancer models. All other chemicals and solvents were of analytical grade or high performance liquid chromatographic (HPLC) grade. Pure water prepared with the Heal Force Pure Water System and was always used.