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Biomedical subjects

S J Yu

Publications and source records attributed to S J Yu.

12 recordsLinked to original sources

Expression of CYP1A1 gene in patients with lung cancer: evidence for cigarette smoke-induced gene expression in normal lung tissue and for altered gene regulation in primary pulmonary carcinomas.

The major polycyclic aromatic hydrocarbon inducible-cytochrome P4501A1 gene (CYP1A1) is presumed to be important in pulmonary carcinogenesis and toxicology because its product, the cytochrome P4501A1-dependent (CYP1A1-dependent) monooxygenase, transforms selected xenobiotics (including polycyclic aromatic hydrocarbon procarcinogens in cigarette smoke) to potent carcinogenic metabolites. CYP1A1 messenger RNA (mRNA) expression has not, however, been previously demonstrated in human pulmonary tissue. This report defines CYP1A1 gene expression in normal lung tissue and primary pulmonary carcinoma tissue obtained at thoracotomy from 56 patients with lung cancer. When Northern blot hybridization analyses were performed, 17 of 19 (89%) and zero of five (0%) samples of normal lung tissue from active cigarette smokers and nonsmokers, respectively, expressed the normal 2.8-kilobase CYP1A1 mRNA. In addition, a time-dependent decrease in expression of the CYP1A1 gene was noted in normal lung tissue from individuals who were former smokers, with a decrease in expression occurring as early as 2 weeks following cessation of cigarette smoking. Expression became undetectable in all patients who had stopped smoking more than 6 weeks prior to study. When CYP1A1 gene expression was evaluated in lung cancers, mRNA levels were detectable in one of four (25%) tumors from nonsmokers; two of 24 (8%) tumors from former smokers; and seven of 15 (47%) tumors from cigarette smokers. In addition, an approximately 10-kilobase CYP1A1 RNA species, which was not detectable in normal lung tissue, was observed in five of ten (50%) of the lung cancers that expressed the CYP1A1 gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytochrome P-450 CYP1A1

Altered regulation of the cytochrome P4501A1 gene: novel inducer-independent gene expression in pulmonary carcinoma cell lines.

The cytochrome P450 (CYP) systems catalyze the metabolic transformation of a wide variety of xenobiotics including procarcinogens present in cigarette smoke condensate as well as atmospheric pollutants. The CYP1A1 isoenzyme is of particular interest because it has been implicated as a risk factor in the etiology of lung cancer in heavy cigarette smokers. The identification and expression of the structural CYP1A1 gene in either normal human lung or lung cancer cells has not been reported. Because of its potential significance in human lung cancer, we investigated the expression of the CYP1A1 structural gene in 24 established human lung cancer cell lines including 15 non-small cell (eight adenocarcinomas, three large cell undifferentiated carcinomas, two bronchioloalveolar cell carcinomas, and two squamous cell carcinomas) and nine small cell lung carcinomas. CYP1A1 mRNA was detected in 14 of 15 (93%) of the non-small cell lung carcinoma cell lines examined following 24-hour treatment with benz[a]anthracene (BA) and in nine of 15 (60%) of the non-small cell lines cultured without an inducer in the medium. When the small cell lung cancer lines were evaluated for CYP1A1 gene expression, two of nine (22%) expressed detectable CYP1A1 mRNA in both BA-induced cell cultures and constitutive (control) cultures. A positive correlation was noted between BA-induced CYP1A1 mRNA levels and the corresponding aryl hydrocarbon hydroxylase activity expressed as absolute BA-induced enzyme activity (r = 0.74; P less than .01; n = 24), which further demonstrated that CYP1A1 mRNA expression reflects CYP1A1 enzyme activity in the individual cell lines. These observations represent the first known demonstration of constitutive (non-induced) CYP1A1 gene expression in human cells and suggest altered regulation of the CYP1A1 gene in selected lung cancer cell lines. These human pulmonary carcinoma cell lines, which have documented regulatory defects, could be useful for further identification of the mechanisms associated with CYP1A1 gene regulation.

Adenocarcinoma

Presacral myelolipoma: case report with computed tomographic and angiographic findings.

A rare case of presacral myelolipoma in an otherwise healthy 53 year old man is described. His only complaint was lower abdominal discomfort. Full investigation including computed tomography and angiography revealed a well-delineated, heavily calcified, avascular retrorectal mass adhering to the presacral fascia. Histologically the mass showed a mixture of haemopoietic tissue and mature fat cells. Clinically the absence of symptoms and bone involvement served to distinguish this condition from other more sinister presacral lesions, particularly a chordoma.

Angiography

Cytochrome P-450-dependent monooxygenase activity in the velvetbean caterpillar, Anticarsia gemmatalis Hübner.

The activity of microsomal aldrin epoxidase was observed in various tissues of the last instar larva of the velvetbean caterpillar (Anticarsia gemmatalis Hübner) with the midgut being the most active. Optimum conditions for assaying the enzyme were established. Allelochemicals (monoterpenes, indoles and flavones) and host plants (cowpeas, cotton, peanuts, soybeans and hairy indigo) were found to induce the monooxygenase. Piperonyl butoxide decreased and increased the toxicity of methomyl and methyl parathion, respectively, suggesting that the monooxygenase system of velvetbean caterpillars plays a major role in the detoxification of xenobiotics.

Animals

Abnormalities in the microsomal oxidases of the WHO standard reference strain of Musca domestica.

Observations made during biochemical and toxicological studies of the housefly, in which the WHO standard reference (SR) strain was used as a standard, indicated that this strain differs from other strains in certain physiological and toxicological aspects. Experiments are described in which microsomal oxidases prepared from the standard reference strain and several other housefly strains, both susceptible and resistant to insecticides, were compared for heat stability, sensitivity to ionic strength, pH optima, and the spectral characteristics of their cytochrome P-450. In a comparison with 8 strains the SR strain microsomes were more stable at high incubation temperatures (40-47.5 degrees C). Compared to two other strains (NAIDM, susceptible, and Isolan-B, resistant) SR was more stable at low pH and more sensitive to high ionic strength. In spectral comparisons with NAIDM and Isolan-B, SR was found to contain microsomal cytochrome P-450 that differed slightly in its carbon monoxide or octylamine binding spectra. The results suggest that this strain may not provide a suitable reference in studies involving the microsomal oxidases. However, these apparent differences should not reduce the value of the SR stain as a reference in insecticide resistance studies.

Aldrin