Household cooking oil type and risk of oral micronucleus frequency in Chinese nonsmokers.

Household animal fat has been linked to increased incidence of cancers compared with vegetable fat. However, few epidemiological studies have associated these two cooking oil types with precancerous genotoxic effects, such as occurrence of micronuclei (MN). This study aimed to explore the association between oral MN frequency and household cooking oil type and whether the association can be attributed to polycyclic aromatic hydrocarbons (PAHs). We collected information about individual cooking oil use, measured genotoxic effects by MN tests and urinary PAHs metabolites (OHPAHs) in 245 nonsmokers. The associations between household cooking oil type and MN frequency and OHPAHs were analyzed using generalized linear models (GLMs) and logistic regression models, evaluating odds ratios and coefficient (95% confidence intervals) (ORs, 95% Cls; ß, 95% Cls). The odds of animal fat consumers, rather than vegetable fat consumers, was positively associated with higher MN frequency (OR = 1.94, P < 0.05). The associations were discovered in participants only using kitchen ventilation (OR = 2.04, P < 0.05). Animal fat consumers had higher total OHPAHs than vegetable fat consumers (1.58 ± 0.22 mg/mol, Cr vs 1.20 ± 0.12 mg/mol, Cr; P = 0.028). Significant correlations were observed between total OHPAHs quartiles and increased MN frequency (ß = 0.38, P-trend = 0.026). After stratifying by household cooking oil type, sensitivity analyses showed that the positive association between total OHPAHs quartiles and increased MN frequency was only observed in animal fat consumers (ß = 0.61, P-trend = 0.030). In conclusion, usage of household animal fat was associated with an increased odds of oral MN frequency in Chinese nonsmokers and the odds correlated with increased PAHs exposure. This finding supplemented evidence associating cooking oil type with genotoxic effects and explained its association with PAHs exposure.

TIMP3/TGF­ß1 axis regulates mechanical loading­induced chondrocyte degeneration and angiogenesis.

Chondrocytes in injured cartilage tissue are susceptible to mechanical loading; mechanical overloading can induce cartilage degeneration. The aim of the present study was to investigate whether mechanical loading can regulate chondrocyte degeneration and angiogenesis via the tissue inhibitor of matrix metalloproteinase­3 (TIMP3)/transforming growth factor (TGF)­ß1 axis. Primary human chondrocytes were obtained from knee articular cartilage of a healthy donor. Then, normal chondrocytes or TIMP3 lentivirus­transfected (LV­TIMP3) chondrocytes were subjected to mechanical loading (10 MPa compression). Then, chondrocytes were stimulated with 1 µg/ml lipopolysaccharide (LPS) or treated with LDN­193189 (inhibitor of TGF­ß1 signaling pathway). In addition, human umbilical vein endothelial cells (HUVECs) were co­cultured with chondrocytes or LV­TIMP3 chondrocytes. The expression levels of collagen­I, proteoglycan, TIMP3, TGF­ß1, Smad2 and Smad3 were detected by reverse transcription­quantitative PCR and western blotting. Moreover, cell apoptosis and viability were determined using flow cytometry and MTT analysis, while cell migration was observed by Transwell assays. In addition, the vascular endothelial growth factor (VEGF)/VEGF receptor (R)2 binding rate in HUVECs was detected by a solid­phase binding assay. It was demonstrated that mechanical loading significantly inhibited the expression levels of collagen­I and proteoglycan in chondrocytes, as well as reducing cell proliferation and promoting cell apoptosis. In addition, the expression levels of TIMP3, TGF­ß1, phosphorylated (p)­Smad2 and p­Smad3 were significantly decreased in degenerated chondrocytes that were induced by LPS, as well as in chondrocytes treated with LDN­193189. Furthermore, TIMP3 overexpression suppressed cell migration and reduced the VEGF/VEGFR2 binding rate in HUVECs. Mechanical loading significantly inhibited the expression levels of TIMP3, TGF­ß1, p­Smad2 and p­Smad3 in chondrocytes, and also increased cell migration of HUVECs; TGF­ß1 treatment or TIMP3 overexpression reversed these effects. Thus, the TIMP3/TGF­ß1 axis may be a vital signaling pathway in mechanical loading­induced chondrocyte degeneration and angiogenesis.