STAM-binding protein regulates melanoma metastasis through SLUG stabilization.

STAM-binding protein, STAMBP, is a JAMM-family deubiquitinating enzyme containing the microtubule-interacting/transport domain and STAM-binding domain. Although the biological importance of STAMBP in development has been recognized because the microcephaly-capillary malformation syndrome in human is caused by its somatic mutations, the role of STAMBP in cancer has not yet been determined. In this study, we demonstrate that STAMBP is a key molecule for regulating melanoma migration and invasion, but not survival, by knocking down STAMBP in vitro. STAMBP regulates SLUG expression through a post-transcriptional mechanism to control protein stability and further contributes to the in vivo metastatic potential of melanoma. Collectively, these results indicate the importance of STAMBP in melanoma metastasis by regulating SLUG. It is therefore a potential therapeutic target.

Concentrations and human health risk assessment of organochlorine pesticides in edible fish species from a Rift Valley lake-Lake Ziway, Ethiopia.

Fish consumption is known to have several health benefits for humans. However, the accumulation of organic pollutants, like organochlorine pesticides (OCPs) could pose health hazards. Thus, OCPs in edible fish species (Oreochromis niloticus, Tilapia zillii, Carassius spp., and Clarias gariepinus) from Lake Ziway, an Ethiopian Rift Valley Lake were investigated to assess the potential human health hazards of these contaminants. Dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs), chlordanes, and heptachlors were observed with ΣOCPs concentration ranging from 1.41 to 63.8 ng g(-1) ww. DDTs were the predominant contaminants (0.9 to 61.9 ng g(-1) ww), followed by HCHs. The predominance of DDTs may be attributed to their current use in vector control and contamination from past usage. The estimated daily intakes (EDIs) of OCPs from all fish species were much lower than the acceptable daily intakes (ADIs), indicating that consumption of fish is at little risk to human health at present. However, the cancer risk estimates in the area of concern and the hazard ratios (HRs) of HCHs, DDTs, and heptachlors exceeded the threshold value of one, indicating daily exposure to these compounds is a potential concern. This may result in a lifetime cancer risk greater than of 1 in 10(6).

Middle ear effusion and fungi.

OBJECTIVES: Bacteria and viruses are rarely isolated from the middle ear fluid in cases of otitis media with effusion (OME). However, since endotoxins are often detected in such effusions, it is suspected that patients with OME have a previous history of gram-negative infection. Recently, fungi have drawn attention as microorganisms that cause chronic sinusitis. We investigated the involvement of fungi in the formation of middle ear effusions of patients with OME and eosinophilic otitis media, in which patients have viscous middle ear effusions and a history of adult bronchial asthma indicating definite involvement of eosinophils. METHODS: Middle ear effusions and nasal secretions were collected from patients with eosinophilic otitis media (7 patients) or OME (12 patients), and smears were prepared for methenamine silver staining. The remaining specimens were embedded in Epon and stained with toluidine blue for observation under a light microscope, and ultrathin sections were prepared for examination under an electron microscope. RESULTS: Fungal hyphae were detected in the middle ear fluid in all of the patients with eosinophilic otitis media or OME. Charcot-Leyden crystals (CLCs) were observed in 6 of the 7 patients with eosinophilic otitis media. In regard to the findings in the nasal secretions, fungal hyphae were also detected in the nasal secretions of all patients, whereas CLCs were detected in only 1 patient with eosinophilic otitis media. CONCLUSIONS: It was clarified by use of the methenamine silver staining method that fungi were present in the middle ear fluid in 100% of the studied cases of eosinophilic otitis media or OME. Whether fungi are also present in the middle ear cavity of normal persons is unknown, but the possibility that they may contribute as a cause of both diseases cannot be excluded. Particularly in eosinophilic otitis media, the observation of numerous CLCs in the middle ear fluid suggests that many eosinophils have degenerated. The eosinophil granule proteins released from the degenerated eosinophils can cause epithelial injury of the middle ear. The possibility that fungi induce the eosinophils in the middle ear also cannot be excluded.

Melanogenesis-inhibitory and cytotoxic activities of diarylheptanoids from Acer nikoense bark and their derivatives.

Nine cyclic diarylheptanoids, 1-9, including two new compounds, i.e., 9-oxoacerogenin A (8) and 9-O-ß-D-glucopyranosylacerogenin K (9), along with three acyclic diarylheptanoids, 10-12, and four phenolic compounds, 13-16, were isolated from a MeOH extract of the bark of Acer nikoense (Aceraceae). Acid hydrolysis of 9 yielded acerogenin K (17) and D-glucose. Two of the cyclic diarylheptanoids, acerogenin A (1) and (R)-acerogenin B (5), were converted to their ether and ester derivatives, 18-24 and 27-33, respectively, and to the dehydrated derivatives, 25, 26, 34, and 35. Upon evaluation of compounds 1-16 and 18-35 for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α-melanocyte-stimulating hormone (α-MSH), eight natural glycosides, i.e., six diarylheptanoid glycosides, 2-4, 6, 9, and 12, and two phenolic glycosides, 15 and 16, exhibited inhibitory activities with 24-61% reduction of melanin content at 100 µM concentration with no or almost no toxicity to the cells (88-106% of cell viability at 100 µM). In addition, when compounds 1-16 and 18-35 were evaluated for cytotoxic activity against human cancer cell lines, two natural acyclic diarylheptanoids, 10 and 11, ten ether and ester derivatives, 18-22 and 27-31, and two dehydrated derivatives, 34 and 35, exhibited potent cytotoxicities against HL60 human leukemia cell line (IC(50) 8.1-19.3 µM), and five compounds, 10, 11, 20, 29, and 30, against CRL1579 human melanoma cell line (IC(50) 10.1-18.4 µM).

Melanogenesis inhibitory activity of monoterpene glycosides from Gardeniae Fructus.

A new iridoid glycoside, 10-O-(4"-O-methylsuccinoyl)geniposide (7), and two new pyronane glycosides, jasminosides Q and R (13 and 14, resp.), along with nine known iridoid glycosides, 1-6 and 8-10, and two known pyronane glycosides, 11 and 12, were isolated from a MeOH extract of Gardeniae Fructus, the dried ripe fruit of Gardenia jasminoides (Rubiaceae). The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of compounds 1-14 on the melanogenesis in B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), three compounds, i.e., 6-O-p-coumaroylgeniposide (3), 7, and 6'-O-sinapoyljasminoside (12), exhibited inhibitory effects with 21.6-41.0 and 37.5-47.7% reduction of melanin content at 30 and 50 µM, respectively, with almost no toxicity to the cells (83.7-106.1% of cell viability at 50 µM).

Melanogenesis inhibitory activity of sesquiterpenes from Canarium ovatum resin in mouse B16 melanoma cells.

Four known sesquiterpene alcohols, i.e., 1-4, ten triterpene alcohols, i.e., 5-14, and four triterpene acids, i.e., 15-18, were isolated from the MeOH extract of Canarium ovatum resin (elemi resin). Upon evaluation of the previously described compounds 1-18 on the melanogenesis in B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), three sesquiterpene alcohols, i.e., cryptomeridiol (1), 4-epicryptomeridiol (2), and cadin-1(14)-ene-7α,11-diol (4), exhibited inhibitory effects with 27.4-34.1 and 39.0-56.9% reduction of melanin content at 50 and 100 µM, respectively, with no or very low toxicity to the cells (80.9-103.9% of cell viability at 100 µM). Western-blot analysis revealed that compounds 1 and 2 reduced the protein levels of MITF (=microphtalmia-associated transcription factor), tyrosinase, and TRP-2 (=tyrosine-related protein 2), mostly in a concentration-dependent manner, suggesting that these compounds exhibit melanogenesis inhibitory activity on α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of tyrosinase and TRP-2. Three sesquiterpene alcohols, i.e., 1, 2, and 4, are, therefore, considered to be valuable as potential skin-whitening agents.

Glycosidic inhibitors of melanogenesis from leaves of Momordica charantia.

Eight glycosidic compounds, 1-8, including two new compounds, (4ξ)-α-terpineol 8-O-[α-L-arabinopyranosyl-(1→6)-ß-D-glucopyranoside] (5) and myrtenol 10-O-[ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranoside] (7), were isolated from the BuOH-soluble fraction of a MeOH extract of Momordica charantia leaves. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses and comparison with literature. Upon evaluation of compounds 1-8 on the melanogenesis in B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), these compounds were found to exhibit inhibitory activities with 7.1-27.0% and 23.6-46.4% reduction of melanin content at 30 µM and 100 µM, respectively, with no or almost no toxicity to the cells (80.0-103.5% of cell viability at 100 µM). Western blot analysis showed that compound 7 reduced the protein levels of MITF, tyrosinase, TRP-1, and TRP-2 mostly in a concentration-dependent manner, suggesting that this compound inhibits melanogenesis on the α-MSH-stimulated B16 melanoma cells by, at least in part, inhibiting the expression of MITF, followed by decreasing the expression of tyrosinase, TRP-1, and TRP-2.

Bacterial Communities in Various Parts of Air-Conditioning Units in 17 Japanese Houses.

HVAC systems have a significant impact on the indoor environment, and microbial contamination in HVAC systems has a significant effect on the indoor air quality. In this study, to gain a better understanding of the microbial contamination inside ACs, we used NGS to analyze the 16S rRNA gene of bacteria adhering to AC filters, cooling coils, fans, and air outlet surfaces. The five phyla in terms of the highest relative abundance were Proteobacteria, Firmicutes, Actinobacteria, Cyanobacteria, and Bacteroidetes. The surface of an AC filter provides a history of indoor airborne bacterial contamination, and of the 10 bacterial genera we detected with the highest abundance (in the following order: Pseudomonas > Staphylococcus > Paracoccus > Corynebacterium > Acinetobacter > Streptococcus > Methylobacterium > Enhydrobacter > Sphingomonas > Actinotignum) on the filter surface, the top 6 genera were Gram-negative bacteria. Furthermore, the seventh-most abundant genus adhering to the filter surface (Methylobacterium) was the second-most abundant genus on the cooling coil and fan, and the ninth-most abundant genus on the air filter (Sphingomonas) was the third-most abundant genus on the cooling coil. Various factors impact the bacterial flora inside AC units, including the location of the house, AC unit usage, and occupant activity.

Comparison of plasma concentrations of estradiol-17ß and progesterone, and conception in dairy cows with cystic ovarian diseases between Ovsynch and Ovsynch plus CIDR timed AI protocols.

The objectives of this study were 1) to determine the effects of adding a CIDR to the Ovsynch protocol on plasma concentrations of estradiol-17ß and progesterone and conception in dairy cows with cystic ovarian diseases and 2) to examine associations among the estradiol-17ß and progesterone concentrations and conception. Cows were diagnosed as having cystic ovarian diseases if they were found to have a cystic follicle (diameter ≥25 mm) without a corpus luteum by two palpations per rectum with an interval for 7 to 14 days. They were treated with either the Ovsynch (GnRH on Day 0, PGF(2α) on Day 7 and GnRH on Day 9, with AI on Day 10; n=15) or Ovsynch+CIDR protocol (Ovsynch protocol plus a CIDR from Day 0 to Day 7; n=23). Plasma estradiol-17ß concentrations were determined on Days 0, 7 and 9, and plasma progesterone concentrations were determined on Days 0, 7, 9 and 17. The plasma estradiol-17ß and progesterone concentrations at all of the days examined and conception rates did not differ significantly between the two timed AI protocols. The progesterone concentrations on Day 17 and conception rates were lower (P<0.05) for cows with low concentrations of estradiol-17ß (<2 pg/ml) on Day 9 than for cows with high concentrations of estradiol-17ß (≥2 pg/ml). The present study suggests that, in dairy cows with cystic ovarian diseases, addition of a CIDR to the Ovsynch protocol had no remarkable effects on plasma estradiol-17ß and progesterone concentrations during and after the treatments or on conception after timed AI. This study indicates that the low plasma estradiol-17ß concentration at the second administration of GnRH in the protocols can be a predictor for impaired luteal formation and lower likelihood of pregnancy in dairy cows with cystic ovarian diseases.

Avian interspecific differences in VKOR activity and inhibition: Insights from amino acid sequence and mRNA expression ratio of VKORC1 and VKORC1L1.

Worldwide use of anticoagulant rodenticides (ARs) for rodents control has frequently led to secondary poisoning of non-target animals, especially raptors. In order to suggest some factors that may help considering the mechanism of the incidents, this study focused on the avian vitamin K 2, 3-epoxide reductase (VKOR) that is the target protein of ARs. We addressed the interspecific differences in VKOR activity and inhibition related to amino acid sequence and mRNA expression of VKORC1 and VKORC1-like1 (VKORC1L1). Poultry have been considered to be more tolerant to ARs than mammals. However, VKOR activity of owls, hawks, falcon and surprisingly, canaries, was lower and inhibited by warfarin more easily than that of chickens and turkeys. The amino acid sequence of VKORC1 and VKORC1L1 implied that the value of Ki for VKOR activity to ARs could depend on the amino acid at position 140 in the TYX warfarin-binding motif in VKORC1, and other amino acid mutations in VKORC1L1. The mRNA expression ratio of VKORC1:VKORC1L1 differed between turkey (8:1) and chicken (2:3) liver. VKORC1L1 has been reported to be resistant to warfarin compared to VKORC1. Hence, both the Ki of specific VKORC1 and VKORC1L1, and the mRNA expression ratio would cause avian interspecific difference of the VKOR inhibition. Our study also suggested the high inhibition of VKOR activities in raptors and surprisingly that in canaries as well. These factors are the most likely to contribute to the high sensitivity to ARs found in raptors.

[Effects of topical Dry Nose Spray on the transepithelial water loss and potential difference in human nasal mucosa].

BACKGROUND: Nasal airway is the entrance to the respiratory tract. The upper airway has function of humidification and secretion. We have already demonstrated the human nasal mucosal water loss as the transepithelial water loss. The aim of this study is to evaluate the short term effect of DryNose TM Spray on the transepithelial loss and alteration of potential difference (PD) in human nasal mucosa. METHODS: Measurement of transepithelial water loss of nasal mucosa (TEWL) was performed on the inferior nasal turbinate by using Tewamerter TM210 (Courage + Khasaka electric, Germany). PD was measured using the Ussing's technique. RESULTS: The significant decrease in TEWL was observed after spray. On the other hands, PD did not change after spray. CONCLUSION: The effects of topical application of DryNose Spray on nasal mucosa decreased water loss.

[Characterization of eosinophils in soft tissue eosinophilic granuloma].

BACKGROUND: Soft tissue eosinophilic granuloma assumes the form of a poorly-demarcated painless mass, and is characterized by marked eosinophil infiltration. Although this tumor decreases in size in response to steroid therapy, it grows again after discontinuation of it, and ultimately proves intractable to treatment. We recently attempted to characterize electron-microscopically the eosinophils in the area affected by soft tissue eosinophilic granuloma. METHODS: Needle biopsy of subauricular masses was carried out before and after steroid treatment. The collected tissue was observed under an electron microscope. RESULTS: Before treatment, more than 90% of the eosinophils constituting the granulation tissue had a broken cell membrane. A number of Charcot-Leyden crystals were noted in the intercellular spaces. Following steroid treatment, more than 90% of eosinophils were intact, and Charcot-Leyden crystals were no longer observed. CONCLUSION: These findings suggest that destruction of eosinophils within granulation tissue aggravates soft tissue eosinophilic granulom.

COP9 signalosome subunit 5 regulates cancer metastasis by deubiquitinating SNAIL.

Cancer metastasis is a major cause of mortality in cancer patients. The transcription factor SNAIL plays an important role in cancer metastasis and progression, and its expression is tightly regulated by the ubiquitin-proteasome system through the balance between ubiquitin ligases and deubiquitinating enzymes. While several ubiquitin ligases of SNAIL have been identified, it is not yet clear regarding deubiquitinating enzyme. In this study, we identified COP9 signalosome subunit 5 (COPS5) as a deubiquitinating enzyme of SNAIL by using siRNA library screening. COPS5 downregulation significantly reduced the expression of SNAIL and impaired the metastatic potential of lung cancer cells both in vitro and in vivo. Importantly, we demonstrated that COPS5 binds to SNAIL and stabilizes its expression by deubiquitination. Furthermore, we observed the positive correlation between COPS5 and SNAIL expression in the clinical tissue samples of lung adenocarcinomas by using tissue microarray analysis. These findings provide strong evidence that COPS5 can be a new therapeutic target for cancer metastasis as a deubiquitinating enzyme of SNAIL.

Hypertonic saline alters electrical barrier of the airway epithelium.

OBJECTIVE: The effect of tonicity changes in nebulizer solutions and irrigations on nasal mucosa is not well known. The present study aims to determine the basic mechanism of hypertonic solution on airway epithelial barrier. STUDY DESIGN AND SETTING: We investigated the electrical potential difference (PD) that is influenced by both active transport and the transepithelial electrical resistance of the epithelial mucosa in the human nose in vivo. The short circuit current (SCC) revealed net ion transport across the epithelium in the guinea pig trachea in vitro. Finally, the size dependency of macromolecules across the tracheal mucosa was determined in vitro using FITC-labeled dextrans of different sizes. RESULTS: PD was significantly decreased after topical application of hypertonic solution both in human and in guinea pig nose. SCC was significantly decreased after application of hypertonic solution. The transport of these dextrans from the basolateral to the apical side was not increased significantly after apical application of hypertonic saline. CONCLUSIONS: Hypertonic saline enhances the electrical permeability of the airway epithelial mucosa but not transport of macromolecule in the short term.

Oncocytic carcinoma of the nasal cavity with widespread lymph node metastases.

The first case of oncocytic carcinoma which arose from the inferior turbinate of the nasal cavity with orbital invasion through the nasolacrimal canal and widespread lymph node metastases in the neck and face is reported here. The tumor metastasized rapidly, spread widely to the whole neck and face, and produced tumor emboli in the lymphatics and extranodal extension by rupture of the lymph node capsule in the absence of clinically palpable regional lymph node enlargement. We think the oncocytic carcinoma of the nasal cavity may be a high-grade malignancy tumor.

[A case of the esophageal candidiasis supposedly caused by rhinenchysis steroid chronic administration before sleep].

UNLABELLED: In general, steroid is mainly used as anti-inflammatory action in case of allergic diseases. As one of the side effects of inhalation steroid, a report is given below regarding buccal capsule/esophageal candidiasis. The patient came to the hospital with the chief complaint regarding passage dysphagia in the time of deglutition; pharyngitis and esophageal candidiasis were found by endoscopy of upper gastrointestinal tract.The interview after the endoscopy revealed that the patient, a 69-year-old female was diagnosed as chronic perennial allergic rhinitis a few years ago, and had been inhaling rhinenchysis Beclometasone dipropionate (BDP) before sleep every day for the past two years because using this collunarium seemed to mitigate the nasal obstruction and mucus during sleep. The patient did not report this fact before the endocsopy because she did not associate it with her subjective symptom. In this case, it was assumed that nebulized rhinenchysis BDP was accidentally swallowed to the pharynx and esophagus during sleep. As a treatment, rhinenchysis BDP was canceled and instead Azunol mouth washing (gargling/nasal douche) was used. No antifungal agent was used. In two weeks, the patient reported some improvement, and this was confirmed by reexamination of the upper gastrointestinal tract using endoscope in one month and a half. Pharyngitis was improved, and in the digital endoscopic assessment of esophageal candidiasis complicating inhaled steroid therapy the esophageal candidiasis became Grade I (mild grade). As for the later progress, the patient did not report any subjective symptoms such as nasal obstruction and dysphagia. In addition, the inflammation caused by candidiasis and found in the early examination was improved. The patient in this case was under treatment for thrombosis in the vein of lower extremity, but no complications such as diabetes mellitus or immune deficiency syndrome were observed. DISCUSSION: Esophageal candidiasis by chronic administration of inhalation of steroid before sleep for asthmatic patients has been reported. However, there has not been a report of esophageal candidiasis by chronic administration of rhinenchysis steroid before sleep for patients with allergic rhinitis. Similarly, in the case of the use of steroid in the form of collunarium before sleep, steroid stayed in the esophagus via the transendothelial nasal cavity, and that seemed to cause, in the long run, to develop esophageal candidiasis. CONCLUSIONS: One of the implications of the above case is that collunarium can go down, even when it is nebulized in the nasal cavity, to the esophagus via the nasal cavity to buccal capsule. This suggests the necessity for preventative measures in the case of chronic administration of steroid as follows. A. Blowing of the nose just after the use of collunarium B. Daily rinsing (gargling and nasal douche).

[Characteristics of migrating cells in effusion of the middle ear in patients with "eosinophilic otitis media"].

Otitis media with effusion (OME) is known to be a disease that frequently afflicts children. Recently, numerous reports of intractable OME associated with bronchial asthma have been reported, generally referred to as "eosinophilic otitis media". To comprehend the cause and pathogenesis of this disease, we conducted an electron-microscope analysis of the effusion. The subjects were 5 male and 1 female patients, 4 had aspirin-induced asthma and 2 had adult-onset asthma. The number of collapsed and intact eosinophils and other inflammatory cells in the middle ear effusion were counted, and their characteristics were reviewed. Most eosinophils in the middle ear effusion were collapsed, and a high percentage of eosinophils in the nasal discharge were also collapsed. The inflammatory cells were phagocytosed by macrophages at a high frequency in cases of otitis media with effusion, but only a low rate of phagocytosis was observed in cases with eosinophilic otitis media. It is known that necrotic cells are phagocytosed with difficulty, while apoptotic cells are phagocytosed easily by macrophages. Therefore, collapsed eosinophils persist for a long time in middle ear effusion and the released granule proteins from the eosinophils cause the tissue failure. Threfore, we believe that treatment directed at causing apoptosis of eosinophils can prevent exacerbation of the intractable inflammation in this condition.

Effect of steroids on increased permeability of blood vessels of the stria vascularis after auditory ossicle vibration by a drill in otologic surgery.

OBJECTIVES: The vibration caused by drills used for middle ear surgery is considered one of the causes of postoperative sensorineural deafness. Seki et al reported that when drill-induced damage was created in the auditory ossicles of guinea pigs, permeability across the capillary vessels in the stria vascularis increased significantly with the duration of drill-induced vibration. The present study was undertaken to examine changes in permeability across the stria vascularis capillaries following vibration in experimental animals pretreated with steroids, with the goal of developing a method of preventing a vibration-induced increase in permeability across these capillaries. METHODS: After an intravenous dose of hydrocortisone and horseradish peroxidase, the auditory ossicles of guinea pigs were vibrated with a drill for 60 seconds. RESULTS: Intravenous steroid administration before vibration reduced the leakage of horseradish peroxidase from the stria vascularis capillaries after vibration. CONCLUSIONS: The findings suggested that steroids suppress the increase in permeability across the stria vascularis capillaries that results from drill-induced vibration.

[Age distribution of transepithelial water loss in human nasal mucosa].

BACKGROUND: Dry nose is a common complaint in the elderly. Age distribution of transepithelial water loss of human nasal mucosa (TEWL) value was evaluated in this study. METHODS: Eighty-eight volunteers (50 men and 30 women) ranging from 10 to 75 years old were recruited for this study. Measurement of TEWL was performed on the inferior nasal turbinate. TEWL was measured with an evaporation meter applying Fick's law (Tewameter TM 300; Courage and Khazaka, Cologne, Germany). RESULTS: TEWL value tends to increase in order of age, indicating that the barrier function of epithelium may decline with age. CONCLUSION: The measurement of transepithelial water loss should be contributed to assess the efficiency of nasal mucosal barrier disorders in the elderly.

Strain differences in cytochrome P450 mRNA and protein expression, and enzymatic activity among Sprague Dawley, Wistar, Brown Norway and Dark Agouti rats.

Rat cytochrome P450 (CYP) exhibits inter-strain differences, but their analysis has been scattered across studies under different conditions. To identify these strain differences in CYP more comprehensively, mRNA expression, protein expression and metabolic activity among Wistar (WI), Sprague Dawley (SD), Dark Agouti (DA) and Brown Norway (BN) rats were compared. The mRNA level and enzymatic activity of CYP1A1 were highest in SD rats. The rank order of Cyp3a2 mRNA expression mirrored its protein expression, i.e., DA>BN>SD>WI, and was similar to the CYP3A2-dependent warfarin metabolic activity, i.e., DA>SD>BN>WI. These results suggest that the strain differences in CYP3A2 enzymatic activity are caused by differences in mRNA expression. Cyp2b1 mRNA levels, which were higher in DA rats, did not correlate with its protein expression or enzymatic activity. This suggests that the strain differences in enzymatic activity are not related to Cyp2b1 mRNA expression. In conclusion, WI rats tended to have the lowest CYP1A1, 2B1 and 3A2 mRNA expression, protein expression and enzymatic activity among the strains. In addition, SD rats had the highest CYP1A1 mRNA expression and activity, while DA rats had higher CYP2B1 and CYP3A2 mRNA and protein expression. These inter-strain differences in CYP could influence pharmacokinetic considerations in preclinical toxicological studies.