Expression of CYP and GST in human normal and colon tumor tissues.

We investigated the immunohistochemical staining characteristics of cytochrome P450 1A1 (CYP1A1), CYPB1, CYP2E1, and glutathione S-transferase P1 (GSTP1), GSTT1, GSTO1, GSTK1 in colon tumor and surrounding normal colon tissues. Tissues were obtained from 47 patients with colon adenocarcinoma and the staining intensity of tumor and control tissues was compared. CYP1A1, CYP1B1, CYP2E1, GSTP1, GSTT1, GSTO1 and GSTK1 expressions in colon cancer cells were significantly greater than those in normal colon epithelial cells. No significant relation was found between the isoenzyme expressions and age, gender, smoking status, tumor grade and tumor stage. The higher expressions of CYP1A1, CYP1B1, CYP2E1, GSTP1, GSTO1, GSTT1 and GSTK1 in tumor than in normal colon tissues may be important for colon cancer progression and development.

Does maternal exposure to artificial food coloring additives increase oxidative stress in the skin of rats?

Glutathione-S-transferase (GST) and cytochrome P450 family 1 subfamily A polypeptide 1 (CYP1A1) metabolize and detoxify carcinogens, drugs, environmental pollutants, and reactive oxygen species. Changes of GST expression in tissues and gene mutations have been reported in association with many neoplastic skin diseases and dermatoses. Widely used artificial food coloring additives (AFCAs) also reported to effect primarily behavioral and cognitive function and cause neoplastic diseases and several inflammatory skin diseases. We aimed to identify the changes in expression of GSTs, CYP1A1, and vascular endothelial growth factor (VEGF) in rat skin which were maternally exposed AFCAs. A rat model was designed to evaluate the effects of maternal exposure of AFCAs on skin in rats. "No observable adverse effect levels" of commonly used AFCAs as a mixture were given to female rats before and during gestation. Immunohistochemical expression of GSTs, CYP1A1, and VEGF was evaluated in their offspring. CYP1A1, glutathione S-transferase pi (GSTP), glutathione S-transferase alpha (GSTA), glutathione S-transferase mu (GSTM), glutathione S-transferase theta (GSTT), and VEGF were expressed by epidermal keratinocytes, dermal fibroblasts, sebaceous glands, hair follicle, and subcutaneous striated muscle in the normal skin. CYP1A1, GSTA, and GSTT were expressed at all microanatomical sites of skin in varying degrees. The expressions of CYP1A1, GSTA, GSTT, and VEGF were decreased significantly, while GSTM expression on sebaceous gland and hair follicle was increased. Maternal exposure of AFCAs apparently effects expression of the CYP1A1, GSTs, and VEGF in the skin. This prominent change of expressions might play role in neoplastic and nonneoplastic skin diseases.

Expression of GSTM4 and GSTT1 in patients with Tinea versicolor, Tinea inguinalis and Tinea pedis infections: a preliminary study.

BACKGROUND: Several skin diseases are believed to be associated with oxidative stress. Defence against reactive oxygen species in the skin involves a variety of antioxidant enzymes, including glutathione-S-transferases (GSTs) catalysing the reaction between reduced glutathione, and a variety of exogenously and endogenously derived electrophilic compounds. The mammalian soluble GSTs are divided into five main classes: alpha (A), mu (M), pi (P), theta (T) and zeta (Z). AIM: To investigate the expression of GSTM4 and GSTT1 in lesional and nonlesional skin of patients with dermatophytoses and Tinea versicolor infection. Methods. Expression of GSTM4 and GSTT1 was assessed by immunohistochemistry for dermatophytoses in 15 patients with T. versicolor, 15 patients with Tinea pedis and 8 patients with Tinea inguinalis, and compared with healthy controls (n = 9). After written consent was signed by each participant, punch biopsies were excised from the centre of the lesional skin sites in patients and from the normal skin sites in controls. The relationships between expression of GSTM4 and GSTT1 isoenzymes and fungal infections were also examined. RESULTS: When the normal and infected tissue of these cases were compared according to their staining intensity, GSTM4 expression was found to be stronger in control epithelium than in the epithelium of patients with T. pedis, T. inguinalis or T. versicolor (P < 0.05). By contrast, expression of GSTT1 was stronger in the epithelium of patients infected with any of the three dermatophytes than in control epithelium (P < 0.05). CONCLUSIONS: There is a significant relationship between presence of T. versicolor, T. inguinalis and T. pedis and expression of GSTM4 and GSTT1.

GST isoenzymes in matched normal and neoplastic breast tissue.

The potential to metabolize endogenous and exogenous substances may influence breast cancer development and tumor growth. Therefore we investigated GST activity and the protein expression of glutathione S-transferases (GSTs) isoenzymes known to be involved in the metabolism of endogenous and exogenous carcinogens in breast cancer tissue to obtain new information on their possible role in tumor progression. The interindividual variation in the conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) and of 1,2-epoxy-3-(p-nitrophenoxy) propane (EPNP) with glutathione (GSH) by cytosolic glutathione S-transferases (GSTs) were investigated in human breast matched normal and tumor samples. The GSTA, GSTM, GSTP and GSTT isoenzymes from the crude extracts of matched breast normal and tumor tissues in terms of their immunological properties using western blotting were compared. In most of the samples, the GST activities were higher in the tumor than in the normal cytosolic fractions against both CDNB and EPNP. In the western blotting analysis, it was proved statistically that in normal and tumor epithelial cells, there was difference between GST pi and theta isoenzymes expressions (p0.05). In normal epithelium there was a stronger GST theta expression than in invasive tumor tissues (p=0.013). However, the stronger GST pi expression was observed in tumor epithelium than in normal epithelium in human breast cancers (p=0.000). We found the GSTP protein level and GST activities were higher in the breast tumor than in the normal cytosolic fractions against both CDNB and EPNP, thus implicating a certain biological importance.

Isolated itching of external auditory canal: clinicopathological study with immunohistochemical determination of antimicrobial peptides.

OBJECTIVE: This study aimed to demonstrate the histological and immunohistological features of skin biopsy specimens from patients complaining of isolated itching of the external auditory canal. MATERIALS AND METHODS: A prospective, case-control study was performed of 24 patients undergoing evaluation for contact dermatitis of the external auditory canal, and 24 controls. Skin biopsies were examined histologically by a single, blinded dermatopathologist, using light microscopy, to determine histopathological characteristics. The immunohistological presence of the antimicrobial peptides human ß-defensin-3 and LL-37 cathelicidin was also assessed. Findings for patients and controls were compared. RESULTS: There was a statistically significant difference in the degree of inflammation, comparing patients and controls (p < 0.05). There was no significant difference in the presence of spongiotic changes, comparing patients and controls (p > 0.05). Furthermore, the patients' skin biopsies did not show pronounced expression of human ß-defensin-3 or LL-37 cathelicidin. CONCLUSION: Histological and immunohistological examination of skin biopsies from cases of isolated itching of the external auditory canal did not support a diagnosis of dermatitis.