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Biomedical subjects

I C Hsu

Publications and source records attributed to I C Hsu.

At least 55 records · Page 3Linked to original sources
PubMed1979

Induction of ouabain-resistant mutation and sister chromatid exchanges in Chinese hamster cells with chemical carcinogens mediated by human pulmonary macrophages.

Pulmonary macrophages (PAM) metabolically activated benzo[a]pyrene [B(a)P] and its proximate carcinogenic metabolite, (+/-)trans 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (7,8-diol), to ultimate mutagens that were detected in cocultivated Chinese hamster V79 cells. Increases in the frequency of ouabainresistant (O(r)) mutations and sister chromatid exchanges were found in V79 cells only when they were cocultivated with both PAM and the chemical procarcinogens. 7,8-Diol caused higher frequencies of both O(r) mutations and sister chromatid exchanges than did the parent compound, B(a)P. When metabolically activated by PAM the mean O(r) mutation frequency caused by B(a)P was 9 O(r) mutants/10(6) surviving V79 cells per 10(6) PAM and a 10-fold interindividual variation (range, 2-21) was found. The mean O(r) mutation frequency caused by 7,8-diol was 64 and a ninefold interindividual variation (range, 14-120) was found. In the absence of PAM, the O(r) mutation frequency in V79 cells was one or less O(r) mutant per 10(6) survivors. 7,8-Benzoflavone, an inhibitor of mixed function oxidases, reduced the frequencies of O(r) mutations and of sister chromatid exchanges in V79 cells caused by 7,8-diol and B(a)P. As expected 7,8-benzoflavone did not influence the frequency of O(r) mutations caused by one of the ultimate mutagens derived from B(a)P and 7,8-diol, (+/-)7beta, 8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. These data are consistant with the hypothesis that PAM may play a role in the activation of environmental chemical procarcinogens.

Adenocarcinoma↗
PubMed1978

Transfection of Fv-1 permissive and restrictive mouse cells with integrated DNA of murine leukemia viruses.

Whole-cell DNA preparations isolated from SC-1 cells chronically infected with N- or B-tropic murine leukemia viruses (MuLV) were tested for infectious activity in an Fv-1n (NIH-3T3) and two Fv-Ib (C57BL/6 and SV-A31) cell cultures. Efficiency of transfection for all DNAs was better in the NIH-3T3 cells than in C57BL/6 or SV-A31 cells; and an [N-tropic MuLV]SC-1 cell DNA preparation was slightly more infectious than a [B-tropic MuLV]SC-1 cell DNA preparation in all three cell cultures, regardless of their Fv-1 genotypes. Progeny viruses from the transfection showed N- or B-tropism corresponding to that of the parent viruses produced by the infected SC-1 cells that were used for the DNA preparation. DNA dose-response studies in NIH-3T3 cells revealed a one-hit mechanism for both the [B-tropic MuLV]SC-1 cell DNA and the [N-tropic MuLV]SC-1 cell DNA preparation. These results demonstrate that, in contrast to virion infection, transfection of N- and B-tropic MuLV with DNA preparations from chronically infected cells is not affected by the Fv-1 gene.

Cell Line↗
PubMed1978

Human bronchus-mediated mutagenesis of mammalian cells by carcinogenic polynuclear aromatic hydrocarbons.

Cultured human bronchial explants activated benzo[alpha]pyrene (BzaP) into electrophilic metabolites that bind to DNA in bronchial epithelial cells. Promutagenic and mutagenic metabolites of BzaP were also released into the culture medium. An increase in mutation frequency for ouabain resistance was found in Chinese hamster V-79 cells when they were cocultivated with bronchial explants in the presence of BzaP. The proximate carcinogenic form of BzaP, the 7,8-diol [(+/-)-r7,t8-dihyroxy-7,8-dihydrobenzo[a]pyrene], was 5-fold more potent as a promutagen than the parent compound. Neither BzaP nor the 7,8-diol increased the mutation frequency in V-79 cells when they were cultured without bronchial explants. The mutation frequency was directly related to the binding levels of BzaP to bronchial DNA and the concentratin of either BzaP or the 7,8-diol in the medium.

Adenosine Triphosphatases↗
PubMed1977

DNA transfection of ecotropic murine leukemia viruses in mouse cell cultures.

DNA's were isolated from cells chronically infected with N-, B-, or NB-tropic murine leukemia viruses and tested for infectious activity in various mouse cell cultures. Early detection of the DNA transfection is facilitated by growing the DNA-recipient cells in medium containing 10(-6) M hydrocortisone. Appropriate shearing of the DNA preparations may increase the efficiency of the transfection. With these procedures virus production of the transfected cells can be detected by XC plaque assay as early as 4 days after DNA inoculation in NIH 3T3 cells. Susceptibility of the mouse cell cultures to DNA transfection does not parallel their susceptibility to virion infection. Progeny viruses derived from the transfection show the same N- or B-tropic host range property as do the parent viruses.

Animals↗
PubMed1976

Localisation and tissue effects of tritiated dehydroretronecine in young rats.

Sixteen male Spraque-Dawley rats were injected with 3H-dehydroretronecine. The rats were subsequently evaluated for gross and microscopic changes. Scintillation counts and autoradiographic studies of the various organs demonstrated that the pyrrole accumulates in organs which were shown here and by others (Peterson et al; Allen and Hsu) to be affected most severely by dehydroretronecine and dehydroheliotridine. In the present experiment 3H-dehydroretronecine was shown to decrease the growth rate of the rats, decrease the percentage of circulating neutrophils and alter the hepatic mitotic index. Histologically, accumulations of label were seen in the glandular region of the stomach, in the liver, in Huxley's and Henle's layers of the hair follicles and in the epithelial cells lining the convoluted tubules of the kidney. Scintillation counts on the various tissues and autoradiographic evaluations of tissue sections indicate that there is a preferential localisation of radioactivity in the gastric mucosa which is postulated to be related to the pH in this area.

Animals↗
PubMed1976

Tissue distribution, binding properties and lesions produced by dehydroretronecine in the nonhuman primate.

Four-month-old rhesus monkeys were injected with 65 mg of [3H] dehydroretronecine per kg body weight and sacrificed at 6,12 and 24 h following injection. By the 24th h 13% of the dose had been eliminated in the urine. Although there were no feces, the extremely high radioactivity of the bile and intestinal contents suggested this route was a major one for the excretion of this compound. The 3H was distributed throughout the body by the 6th h with the greatest percentage being in the skin and muscle. However, per gram of tissue the gastric mucosa and bile showed the highest radioactivity. Likewise, it was in the gastric mucosa that the lesions produced by dehydroretronecine were the most severe. High levels of radioactivity persisted in the gastric mucosal lysates after washings with trichloroacetic acit (TCA) while only a small percentage of the (3)H remained in the washed liver lysate. It was determined that over 20% of the 3H was bound to mucosal protein and less than 1% to the nucleic acids.

Animals↗
PubMed1976

Neoplastic transformation in tissues of rats exposed to monocrotaline or dehydroretronecine.

Male Sprague-Dawley rats received sc injections biweekly of either the pyrrolizidine alkaloid monocrotaline or its metabolite dehydroretronecine for 1 year. The animals were then observed for an additional 12 months for the induction of neoplasms. Of 60 rats that received dehydroretronecine, 39 developed rhabdomyosarcomas at the injection site, and 5 of these neoplasms metastasized. In the 60 monocrotaline-treated rats, 31 widely dispersed tumors of various cell types were recorded. The reason suggested for the variation in tissue response was that the metabolite dehydroretronecine is a proximate carcinogen, whereas monocrotaline must first be metabolized before its carcinogenic potential is realized.

Animals↗
PubMed1975

Distribution and metabolism of 3H-2,5,2',5'-tetrachlorobiphenyl in rats.

Distribution and metabolism of an isomeric polychlorinated biphenyl were determined in rats. Over 70% of a single dose of 3H-2,5,2',5'-tetrachlorobiphenyl was excreted in the feces and another 13% in the urine during a 14-day period. Adipose tissue, blood, skin, and liver were found to contain low levels of the compound. Over 90% of the excreted tritiated compound was found to be metabolized, the major metabolite being identified as 3-OH-2,5,2',5'-tetrachlorobiphenyl. All of the unmetabolized 2,5,2',5'-tetrachlorobiphenyl was eliminated by the alimentary route.

Adipose Tissue↗
PubMed1975

Urinary metabolites of 2, 5, 2', 5'-tetrachlorobiphenyl in the nonhuman primate.

The metabolism of 2, 5, 2', 5'-tetrachlorobiphenyl (TCB) in nonhuman primates was found to be different from that previously reported in lower species. Monohydroxy TCB (I), the only metabolite in the ether extracts of rat urine, is a minor metabolite in the urine of nonhuman primates. The two major metabolites identified in the urine were dihydroxy TCB (II) and trans-3,4-dihydro-3,4-dihydroxy TCB (III). A second minor metabolite was identified as hydroxy-3,4-dihydro-3,4-dihydroxy TCB (IV). None of the above mentioned metabolites have been reported in primates and only I and III have been identified in lower animals. It is concluded that a likely mechanism for metabolism of TCB in primates is through arene oxide intermediates. This observation is of particular importance in that these types of intermediates are known to alkylate cellular components causing carcinogenic, mutagenic, necrogenic and teratogenic effects.

Animals↗
PubMed1975

Dehydroretronecine-induced rhabdomyosarcomas in rats.

Two groups of rat were given s.c. injections of either monocrotaline or its major detectable metabolite, dehydroretronecine, biweekly for 1 year. Tissues obtained from partial hepatectomies performed at 4 months on a portion of these animals showed that both compounds caused a decided inhibition of mitotic division in regenerating liver. Rhabdomyosarcomas developed at the site of dehydroretronecine injection in 51.6% of the rats and in 3.3% of the monocrotaline-treated rats. Metastatic lesions were recorded in 8.3% of these animals. In addition to the above, 10% of the monocrotaline-treated rats developed other tumors that included myelogenous leukemias, hepatocellular carcinomas, and pulmonary adenomas. These data indicate that either monocrotaline or its metabolite dehydroretronecine are capable of causing neoplastic transformations in the tissues of experimental animals.

Animals↗
PubMed1975

Binding of tritiated dehydroretronecine to macromolecules.

In vivo and in vitro experiments have shown that the pyrrolizidine alkaloid metabolite dehydroretronecine binds readily to macromolecules. In the in vivo experiment there was a preferential binding of dehydroretronecine to the gastric mucosa. Further extraction of the mucosa revealed a large percentage of the 3H was bound to the protein fraction and to a much lesser extent to DNA and RNA. The influence of pH on the binding of dehydroretronecine was substantiated in the in vitro experiment. Dehydroretronecine bound to calf thymus DNA and bovine serum albumin most readily under acidic conditions. These data suggest a direct correlation of the levels of dehydroretronecine binding to cellular macromolecules with the lesions that develop in affected organs.

Animals↗