Biomedical subjects

Toshihiro Kawamoto

Publications and source records attributed to Toshihiro Kawamoto.

At least 19 recordsLinked to original sources

PubMed2007

Susceptibility to inhalation toxicity of acetaldehyde in Aldh2 knockout mice.

In this study, we evaluated the inhalation toxicity of acetaldehyde in Aldh2 KO (Aldh -/-) mice, using pathological method. Male C57BL/6 (Aldh2 +/+) mice and Aldh -/- mice were exposed to atmospheres containing acetaldehyde at levels of 0, 125, and 500 ppm for 24 h/day during 14 days. Although the average blood acetaldehyde concentration of Aldh -/- mice was higher than that of Aldh2 +/+ mice in the acetaldehyde exposure group, observable effects by the acetaldehyde exposure on the lung and liver were not different between wild type and ALDH2 null mice. In Aldh2 -/- mice, the levels of 1) erosion of respiratory epithelium and the subepithelial hemorrhage in nose, 2) hemorrhage in nasal cavity, 3) degeneration of respiratory epithelium in larynx, pharynx and trachea, and 4) degeneration of dorsal skin were higher compared with Aldh2 +/+ mice, indicating that Aldh2 -/- mice are more acetaldehyde-sensitive than Aldh2 +/+ mice. This is the first example for studying pathological effects of Aldh2 deficiency using Aldh -/- mice exposed to a low level of acetaldehyde.

Acetaldehyde↗

PubMed2007

Cytochrome P450 expression (CYP) in non-small cell lung cancer.

The cytochrome P450 (CYP) is associated with tumor development and progression as well as activation of anti-cancer prodrugs and their metabolic clearance. In this study, we investigated the expression of aryl-hydrocarbon receptor (AH-R) and four CYPs (CYP1A1, CYP2A6, CYP2E1 and CYP3A) as putative diagnostic markers in 78 non-small cell lung cancers (NSCLC) along with clinical features of the patients. In non-small cell lung cancer, the expression of the five markers was mainly observed in adenocarcinoma but not in the most squamous cell cancers. The expression of them in adenocarcinoma was more frequent in females than in males, suggesting that a higher risk of women for developing lung adenocarcinoma might be associated with the frequent expression of AH-R and the CYPs. These factors were also more frequently expressed in early stage adenocarcinoma and more differentiated adenocarcinoma. Multiple types of CYPs are more frequently expressed in early stage of adenocarcinoma than in advanced stage of adenocarcinoma. There were positive relationships among AH-R, CYP1A1, CYP2E1 and CYP3A expressions in adenocarcinoma, which suggests a metabolite-mediated cross talk in the gene regulation of these markers. However, any of them was unrelated with the expression of CYP2A6, suggesting that the gene regulation of CYP2A6 in adenocarcinoma may be different from the other three CYPs. The expression frequency of CYP1A1 and CYP2E1 in tumors is independent of their genetic polymorphism. The survival of the patients with advanced adenocarcinoma expressing more than one of CYPs was lower rate than the patients with those expressing no CYPs, suggesting that the expression of the CYPs in advanced adenocarcinoma may be associated with poor survival. Our results suggest that AH-R and 4 CYPs may be good markers for the determination of quality of lung cancer. The information could be useful for the better management of lung cancer by molecular targeting therapy and selection of anti-cancer drug based on individual spectrum of the marker proteins. Therefore, the spectrum of CYP proteins in lung cancer could be useful for changing the present "order-made" therapy to the "tailor-made" therapy.

Adenocarcinoma↗

PubMed2006

A comparison of covalent binding of ethanol metabolites to DNA according to Aldh2 genotype.

In order to clarify the effects of ALDH2 polymorphism on the carcinogenicity and organ damage caused by ethanol consumption, labeled ethanol was administered to wild-type (C57BL/6, Aldh2+/+) and Aldh2 knock-out (Aldh2-/-) mice, and DNA adduct levels of organs were compared according to Aldh2 genotype. Aldh2-/- mice, which have the same genetic background as C57BL/6 mice except in the Aldh2 gene, were used as a model of lack of ALDH2 activity in humans. The DNA adduct levels in liver, stomach, and kidney and radioactivity in liver, stomach, kidney, and serum were measured by liquid scintillation counting 6, 12, and 24h after administration. Though radioactivity levels in all organs decreased over time, there were no significant differences in radioactivity between Aldh2+/+ and Aldh2-/- mice. On the other hand, the DNA radioactivity in each organ tested differed significantly between Aldh2+/+ and Aldh2-/- mice 24h after administration. These findings show that ethanol consumption affects DNA in Aldh2-/- mice much more strongly than in Aldh2+/+ mice. According to the IARC document, ethanol consumption is carcinogenic to humans (Group 1). Moreover, several studies have shown that ALDH2-deficient humans who habitually consume ethanol have higher rates of cancer than humans with ALDH2. Our results support these findings of epidemiological studies.

Aldehyde Dehydrogenase↗

PubMed2006

Smoking cessation program and CYP2A6 polymorphism.

The relationship between CYP2A6 genotype and smoking status remains unclear although several studies have been reported. In this study, we have investigated the significance of CYP2A6 genotype on smoking habit and treatment of nicotine patch. Sixty-one smokers (1.7%) working in a Japanese company (n = 3585) participated in this smoking cessation program. Forty-four of 61 (72.1%) smokers were treated by nicotine patch. A genotyping analysis was carried out for 41 (40 men and 1 women) of 61 participants (67.2%). The smoking cessation rate at 90 days was 54.1% (33/61). Age and smoking years in re-smoking group are significantly lower than those in smoking cessation group. The smoking cessation rate of participants treated with nicotine patch (63.6%; 28/44) was significantly higher than that of the group non-treated with nicotine patch (29.4%; 5/17) at 90 days (p < 0.05). The incidence of homozygotes of CYP2A6 gene deletion (CYP2A619934/19934) in 41 cases (9.8%; 4/41) could be higher than that in 894 healthy controls (3.7%; 33/894) (p = 0.12), while no other variant alleles (CYP2A619932, CYP2A619933 and CYP2A619936) were found. Age and smoking years of participants with CYP2A619934/19934 are significantly higher than those with CYP2A619931 positive. The scores of Fagerstrom test, an analysis for nicotine-dependence, were slightly different between participants with CYP2A619934/19934 and CYP2A619931 positive. Although treatment of nicotine patch is efficacious to smoking cessation, cases with CYP2A619934/19934 might be more sensitive to nicotine adverse effects and more difficult to quit smoking once they have smoking habit.

Administration, Cutaneous↗

PubMed2006

Urinary concentrations of bisphenol A in relation to biomarkers of sensitivity and effect and endocrine-related health effects.

The impact of endocrine-disrupting chemicals (EDCs) on human health is not yet clear because of difficulties in ascertaining their biological effects. In the present study, we evaluated exposure to the EDC, bisphenol A (BPA), in 172 Koreans in relation to biomarkers of susceptibility and effect. The subjects completed questionnaires, which documented occupation, education, lifestyle factors, potential sources of BPA-exposure, and the occurrence of self-diagnosed endocrine disorders. None of the subjects were occupationally exposed to BPA; however, urinary levels of conjugated BPA, determined by HPLC/FD, ranged from 0.03-62.4 microg/l (median, 7.86). The frequencies of potential susceptibility biomarkers, the UGT1A6-Arg184Ser and the SULT1A1-Arg213His polymorphisms, were not associated with urinary BPA levels, either as single genes or in combination. Indirect effects of BPA exposure on the susceptibility to mutagens were evaluated by comparing urinary BPA concentrations with MNNG-induced sister-chromatid exchange (SCE) in lymphocytes cultured from the subjects. BPA exposure showed marginal or significant associations with theSCEs induced by the low doses of MNNG (0-0.4 mM). However, there was no overall association between urinary BPA levels and MNNG-induced frequency at doses ranging from 0.2-0.6 mM. Finally, we did not detect an association between urinary BPA concentration and endocrine-related disorders. Even though we were unable to find a strong association between BPA exposure and a biological response, possibly because of the limited number of subjects, we observed that most of the subjects were exposed to BPA. Therefore, continuous biological monitoring of BPA is a prudent measure to prevent possible BPA-related health risks.

Adult↗

PubMed2006

Hemoglobin adducts as a marker of exposure to chemical substances, especially PRTR class I designated chemical substances.

Many new biomarkers are being studied, in addition to classical biomarkers, such as chemical substances and their metabolites in blood and urine and modified enzymes. Among these new biomarkers, hemoglobin adducts are thought to be especially useful for the estimation of chemical exposures. We review here the use of biomarkers for monitoring exposures to nine substances, mainly focusing on PRTR class I designated chemical substances, styrene, phenyloxirane (styrene oxide), 4,4'-methylendiphenyl diisocyanate (MDI), 4,4'-methylendianiline (MDA), 1,3-butadiene, ethylene oxide, propylene oxide, acrylamide and acrylonitrile. Hemoglobin adduct levels were elevated after exposures to styrene, MDI, MDA, 1, 3-butadiene, ethylene oxide, acrylamide and acrylonitrile. Moreover, hemoglobin adducts of butadiene, ethylene oxide, acrylamide and acrylonitrile have several useful advantages. For example, the hemoglobin adduct of 1,3-butadiene is an even more useful biomarker of exposure than urinary metabolites, and in the case of ethylene oxide, even though the concentration of ethylene oxide-Hb in the blood of workers did not exceed the value of the German exposure equivalent, a significant difference in it was found between workers and a control group. Also hemoglobin adducts of acrylamide and acrylonitrile can reflect their exposures because there are no urinary metabolites of acrylamide and acrylonitrile that are useful for exposure assessment. In addition to these advantages, hemoglobin adducts are superior to DNA adducts with respect to the availability of large amounts, availability of methods for chemical identification, and well-defined life spans due to the absence of repair. Hemoglobin adducts can be effective biomarkers for assessing exposure to and the effects of chemicals.

Biomarkers↗

PubMed2006

Urinary 8-hydoxydeoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA) levels in Aldh2 knock-out mice under acetaldehyde exposure.

To clarify the carcinogenicity of acetaldehyde when associated with ALDH (aldehyde dehydrogenase) 2 polymorphism, Aldh2 knock-out (Aldh2-/-) mice and their wild type (Aldh2+/+) mice were exposed to two different concentrations of acetaldehyde (125 ppm and 500 ppm) for two weeks. Aldh2-/- mice, which have the same genetic background as C57BL/6J (wild mice) except for the Aldh2 gene, were used as models of humans who lack ALDH2 activity. Urinary 8-hydroxydeoxyguanosine (8-OHdG) and plasma malondialdehyde (MDA) levels were measured as indicators of oxidative DNA damage and lipid peroxidation, respectively. At 125 ppm acetaldehyde exposure for 12 d, urinary 8-OHdG levels in Aldh2+/+ mice did not increase. However, urinary 8-OHdG levels in Aldh2-/- mice were slightly increased by the end of the exposure. On the other hand, plasma MDA levels did not increase in either Aldh2-/- orAldh2+/+ mice. At 500 ppm, urinary 8-OHdG levels in both Aldh2-/- and Aldh2+/+ mice significantly increased after 6 and 12 d, but there was no genetic difference. On the other hand, plasma MDA levels in Aldh2+/+ and Aldh2-/- mice did not increase at either 125 ppm or 500 ppm after two weeks of exposure. In conclusion, it is suspected that DNA was damaged by acetaldehyde inhalation, and that susceptibility to acetaldehyde varies according to Aldh2 genotype.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

An essential role for mitochondrial aldehyde dehydrogenase in nitroglycerin bioactivation.

The identity of the cellular mechanisms through which nitroglycerin (glyceryl trinitrate, GTN) elicits nitric oxide (NO)-based signaling to dilate blood vessels remains one of the longest standing foci of investigation and sources of controversy in cardiovascular biology. Recent evidence suggests an unexpected role for mitochondria. We show here that bioconversion by mitochondria of clinically relevant concentrations of GTN results in activation of guanylate cyclase, production of cGMP, vasodilation in vitro, and lowered blood pressure in vivo, which are eliminated by genetic deletion of the mitochondrial aldehyde dehydrogenase (mtALDH). In contrast, generation of vasoactivity from alternative nitro(so)-vasodilators is unaffected. In mtALDH(-/-) mice and their isolated vascular tissue, GTN bioactivity can still be generated, but only at substantially higher concentrations of GTN and by a mechanism that does not exhibit tolerance. Thus, mtALDH is necessary and sufficient for vasoactivity derived from therapeutic levels of GTN, and, more generally, mitochondria can serve as a source of NO-based cellular signals that may originate independently of NO synthase activity.

Aldehyde Dehydrogenase↗

PubMed2005

Immunohistochemical evaluation of cytochrome P450 (CYP) and p53 in breast cancer.

In breast cancer, cytochrome P450 (CYP) metabolizes both endogenous substrates (i.e. estradiol) and exogenous substrates (i.e. anticancer drugs), which is associated not only with tumor development and progression but also with efficacy of cancer treatment. Therefore, we examined the expression of CYPs (CYP2A6, CYP1B1 and CYP3A) and p53 in specimens from 34 Japanese patients with breast cancer by immunohistochemistry. The expression of CYP3A was not detected in the 34 cases. CYP2A6 was detected only in one specimen (2.9%). Twenty-eight specimens (82.4%) showed positive signals for CYP1B1 expression. Eight of 34 (23.5%) were positive for p53 expression. Positive rate of CYP1B1 in stage I disease (100%) was statistically higher than that in stage II - IV disease (70.0%). Positive rate of p53 was 21.4% (6/28) in CYP1B1-positive cases and 33.3% (2/6) in CYP1B1-negative cases. There was no significant relationship between CYP1B1 expression and p53 expression. In conclusion, the expression of CYP3A in breast cancer may be less frequent in Japanese population although the expression of CYP3A has been reported in 20% of breast cancer in Caucasian, suggesting that the CYP3A expression in breast cancer may be dependent on ethnic groups. Since CYP3A is involved in the conversion of tamoxifen to its metabolites, the variation of the CYP3A expression in breast cancer tissues among ethnic groups might cause differences in the efficacy of tamoxifen.

Adult↗

PubMed2005

Expression levels of hepatic cytochrome P450 enzymes in Aldh2-deficient mice following ethanol exposure: a pilot study.

We determined expression levels of hepatic cytochrome P450 (CYP) 2E1, 2B1/2 and 4B1 enzymes in aldehyde dehydrogenase 2 (Aldh2) +/+ and Aldh2 -/- mice by immunoblotting assay following subchronic ethanol exposure for eight days. Using ethanol exposure, the protein expression levels of CYP2E1, 2B1/2 and 4B1 in Aldh2 +/+ mice were increased by factors of 2.61, 1.88 and 2.01 compared with Aldh2 +/+ mice that were not exposed to ethanol, respectively. On the other hand, in the Aldh2 -/- mice, CYP2E1, 2B1/2 and 4B1 protein expression levels after ethanol treatment were shown to be 1.99, 1.05 and 1.33 greater than those of Aldh2 -/- control mice, respectively. We also found an interesting fact in the present study; the Aldh2 -/- mice were shown to have higher CYP2E1 (by a factor of 4.19), 2B1/2 (by a factor of 2.89) and 4B1 (by a factor of 1.53) protein expression levels than Aldh2 +/+ mice despite the lack of ethanol treatment. These results suggest that CYP2E1, 2B1/2 and 4B1 play some role in ethanol metabolism and that Aldh2-deficient individuals may have higher levels of CYP2E1, 2B1/2 and 4B1 enzymes compared to Aldh2 wild-type individuals.

Aldehyde Oxidoreductases↗

PubMed2005

Tissue-distribution of aldehyde dehydrogenase 2 and effects of the ALDH2 gene-disruption on the expression of enzymes involved in alcohol metabolism.

In alcohol metabolism, acetaldehyde, a highly reactive intermediate that may cause cellular and DNA damages, is converted to acetate by mitochondrial aldehyde dehydrogenase ALDH2. Although the majority of ingested alcohol is eliminated in the liver, the first-pass metabolism of ethanol in the upper digestive tract is also important for prevention and management of ethanol-related gastrointestinal diseases. However, the tissue-distribution of Aldh2 in mice has been poorly investigated. In this study, therefore, we investigated the tissue-distribution of Aldh2 as well as Aldh1, Cyp1a1, Cyp2e1, and Cyp4b1 in wild type and Aldh2-null mice by immuno-histochemical analysis. The human liver and esophageal tissues were also examined. In mice, the Aldh2 protein was detected in the liver, lung, heart, kidney, testis, esophagus, stomach, colon, and pancreas, suggesting that the tissue-distribution of Aldh2 in mice is similar to that in humans. Therefore, Aldh2-null mice may be useful model animals for the investigation of alcohol metabolism and related diseases. Compared with the wild type, the expression level of Cyp2e1 was increased in the liver from Aldh2-null mice based on Western blot analysis, whereas the levels of Aldh1, Cyp1a1, and Cyp4b1 were indistinguishable. This observation suggests that a metabolite(s) of Aldh2 might down-regulate the expression of Cyp2e1 gene.

Alcohols↗

PubMed2005

Aldehyde dehydrogenase 2 gene targeting mouse lacking enzyme activity shows high acetaldehyde level in blood, brain, and liver after ethanol gavages.

BACKGROUND: Previously, we created an aldehyde dehydrogenase 2 gene transgenic (Aldh2-/-) mouse as an aldehyde dehydrogenase (ALDH) 2 inactive human model and demonstrated low alcohol preference. In addition, after a free-choice drinking test, no difference in the acetaldehyde level was observed between the Aldh2-/- and wild type (Aldh2+/+) mice. The actual amounts of free-choice drinking were so low that it is uncertain whether these levels are pharmacologically and/or behaviorally relevant in either strain. To elucidate this uncertainty, we compared the ethanol and acetaldehyde concentration in the blood, brain, and liver between the Aldh2-/- and Aldh2+/+ mice after ethanol gavages at the same dose and time. METHOD: We measured differences in the ethanol and acetaldehyde levels between the Aldh2-/- and Aldh2+/+ mice by headspace gas chromatography-mass spectrometry (GC-MS) after ethanol gavages at the same dose and time. RESULTS: Significantly higher blood acetaldehyde concentrations were found in the Aldh2-/- mice than in the Aldh2+/+ mice 1 hr after the administration of ethanol gavages at doses of 0.5, 1.0, 2.0, and 5.0 g/kg. The blood acetaldehyde concentrations in the two strains were 2.4 vs. 0.5, 17.8 vs. 1.9, 108.3 vs. 4.3, and 247.2 vs. 14.0 (microM), respectively. In contrast, no significant difference was observed in the blood ethanol concentrations between the Aldh2+/+ and Aldh2-/- mice. The aldehyde dehydrogenase 2 enzyme metabolized 94% of the acetaldehyde produced from the ethanol as calculated from the area under the curve (AUC) of acetaldehyde when ethanol was administered at a dose of 5.0 g/kg. CONCLUSIONS: These data indicate that mouse ALDH2 is a major enzyme for acetaldehyde metabolism, and the Aldh2-/- mice have significantly high acetaldehyde levels after ethanol gavages.

Acetaldehyde↗

PubMed2005

The effects of 1-nitropyrene on oxidative DNA damage and expression of DNA repair enzymes.

Nitropyrenes (NPs) present in diesel and gasoline emissions are mutagenic and carcinogenic in experimental animals. Nitro-reduction of 1-NP causes oxidative stress. It is unclear whether 8-hydroxydeoxyguanosine (8-OH-dG) is produced from 1-NP and whether it contributes to the carcinogenic activity of 1-NP. In this study, we measured the level of reactive oxygen species (ROS) in cultured human lung epithelial cells after exposure to 1-NP and the intracellular level of 8-OH-dG and expression level of the 8-OH-dG repair enzymes. As results, 1-NP induced the generation of 8-OH-dG via ROS, but 8-OH-dG repair enzymes prevented an increase of 8-OH-dG formation in cellular DNA of the A549 cell line below 250 microM of 1-NP. These data suggest that 1-NP can induce oxidative DNA damage by generation of ROS, which may play a role in the carcinogenesis induced by 1-NP. These data also suggest that individuals with impaired DNA repair enzymes might be more susceptible to lung cancer induced by 1-NP.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2005

Aldehyde dehydrogenase 2 activity affects symptoms produced by an intraperitoneal acetaldehyde injection, but not acetaldehyde lethality.

Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme that oxidizes acetaldehyde. Approximately 45% of Chinese and Japanese individuals are inactive ALDH2 phenotype; acute acetaldehyde toxicity has not been evaluated in these populations. We compared the acute acetaldehyde toxicity between wild-type (Aldh2+/+) and Aldh2-inactive transgenic (Aldh2-/-) mice who were administered an intraperitoneal (ip) injection of a single dose of acetaldehyde. This comparison was made based on the LD(50) values of acetaldehyde and the symptoms following the ip injection. Blood acetaldehyde level was measured in the 400 mg/kg dose group. Immediately after administration of acetaldehyde, the mice exhibited hypoactivity and staggering gait. Subsequently, symptoms such as pale skin, prone position, coma, and abnormal deep respiration were observed. In cases of death, dyspnea, wheezing, and hypothermia were observed from 15 to 30 min after the administration. In cases of survival, crouching, bradypnea, flushing and piloerection were observed. Significant latency of symptom recovery was found in the Aldh2+/- mice as compared with the Aldh2+/+ mice; however, no statistical difference was observed in the acetaldehyde LD(50) values. This might be attributable to the absence of a significant difference in the blood acetaldehyde concentrations in both mice during the first 0-15 min following administration; however, acetaldehyde elimination delay was observed in the Aldh2-/- mice as compared with the Aldh2+/+ mice. Acetaldehyde toxicity difference was observed between the Aldh2+/+ and Aldh2-/- mice; however, no difference in acetaldehyde lethality was observed by administration of a single dose of an ip acetaldehyde injection.

Acetaldehyde↗

PubMed2005

Paired acute inhalation test reveals that acetaldehyde toxicity is higher in aldehyde dehydrogenase 2 knockout mice than in wild-type mice.

Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme that oxidizes acetaldehyde. Approximately 45% of Chinese and Japanese individuals have the inactive ALDH2 genotypes (ALDH2*2/*2 and ALDH2*1/*2); acute inhalation toxicity of acetaldehyde has not been evaluated in these populations. We compared the toxicity between wild-type (Aldh2+/+) and Aldh2-inactive transgenic (Aldh2-/-) mice by using the paired acute inhalation test modified from the acute toxic class method (OECD TG433). Blood acetaldehyde level was measured 4 hr after the inhalation. A pair of Aldh2+/+ and Aldh2-/- mice was put into a chamber and was exposed to 5000 ppm of acetaldehyde. At the start of the inhalation, the mice exhibited hypoactivity and closing of the eyes. Subsequently, symptoms such as crouching, bradypnea, and piloerection were observed. Flushing was observed only in the Aldh2+/+ mice. Symptoms such as tears, straggling gait, prone position, pale skin, abnormal deep respiration, dyspnea, and one case of death were observed only in the Aldh2-/- mice. The symptoms did not change 1 hr after inhalation in the Aldh2+/+ mice. In contrast, in the Aldh2-/- mice, the symptoms became more severe until the end of the inhalation. The blood acetaldehyde level in the Aldh2-/- mice was approximately twice that in the Aldh2+/+ mice 4 hr after inhalation. The Aldh2-/- mice evidently showed more severe toxicity as compared with the Aldh2+/+ mice due to acute inhalation of acetaldehyde at a concentration of 5000 ppm. Acetaldehyde toxicity in Aldh2+/+ and Aldh2-/- mice was estimated and classified one class different. Based on this study, acetaldehyde inhalations were inferred to pose a higher risk to ALDH2-inactive human individuals.

Acetaldehyde↗

PubMed2004

[Exposure to formaldehyde during an anatomy dissecting course].

Formaldehyde is a flammable, colorless and readily polymerized gas at ambient temperature, and is one of the major pollutants in indoor air. Medical students during their dissection course are exposed to formaldehyde, whose exposure is recently considered to be one of the causes of multiple chemical sensitivity. To understand the system that produces exposures and to plan for implementing control options, this study examined formaldehyde exposures that occurred in the gross anatomy laboratory. Formaldehyde in air was sampled by an active 2,4-dinitrophenylhydrazine (DNPH)-silica gel cartridge, extracted with acetonitrile and analyzed with an high performance liquid chromatograph-ultraviolet(HPLC-UV)detector. The geometric mean formaldehyde concentration was 20-93 ppb in the anatomy laboratory before starting the anatomy dissecting. After beginning the dissecting, however, the highest geometric mean concentrations were 1012-1380 ppb. Significant differences were observed during the exposed period for symptoms of "unusual thirst", "burning eyes", "itchy eyes", "bad feeling", "fatigue", etc. in comparison with the non-exposed period. These results show that medical schools should take more concrete measures to reduce exposure to formaldehyde.

Air Pollution, Indoor↗

PubMed2004

Expression of cytochrome P450 in tumor tissues and its association with cancer development.

CYPs (cytochrome P450s) catalyze the conversion of numerous numbers of xenobiotics including carcinogens and drugs. CYPs can be involved in metabolic pathways of activation of procarcinogens and/or inactivation of carcinogens during the tumorigenic processes. Recently, increasing number of cancer tissues as well as normal tissues have been found to express a variety of CYPs. The local expression of CYPs in tumors appears to be very important for the management of cancers since CYPs expressed in tumors may be involved in activation and/or inactivation of anticancer drugs. The expression of CYPs in tumors may also convert endogenous substrates to metabolites that facilitate cancer development. In this review, we summarize the association of CYP expression in cancer tissues with carcinogenesis and cancer treatment.

Antineoplastic Agents↗

PubMed2004

Identification of cytochrome P450 isoforms involved in 1-hydroxylation of pyrene.

Urinary 1-hydroxypyrene (1-OHP) has been used as a biomarker for environmental polyaromatic hydrocarbon (PAH) exposure. However, it is known that there is an interindividual variability in metabolism of pyrene to 1-OHP depending on the activities of the metabolizing enzymes, especially cytochrome P450s (CYPs). In this study, we investigated the 1-hydroxylation of pyrene by 10 forms of cDNA-expressed human P450s in order to identify the principal isoforms of P450s that are involved in the major metabolic pathway of pyrene. The pyrene 1-hydroxylation activity was found to be the highest in CYP1A1 at both 0.5 and 50microM of pyrene, followed by CYP1B1 and 1A2, whereas other enzymes, including CYP2A6, 2C8, 2C9*1, 2C19, 2D6, 2E1, 3A4, and control microsomes, showed very low or undetectable rates of 1-hydroxylation. In conclusion, CYP1A1, 1B1, and 1A2 are major metabolizing enzymes in 1-hydroxylation of pyrene in vitro. This suggests that the individual difference of these enzymes must be included in epidemiological studies to evaluate PAH exposure using urinary 1-OHP.

Aryl Hydrocarbon Hydroxylases↗