Search PubMed⌕ Search

Biomedical subjects

C C Harris

Publications and source records attributed to C C Harris.

At least 379 records · Page 21Linked to original sources
PubMed1980

Metabolism of aflatoxin B1, benzo[a]pyrene, and 1,2-dimethylhydrazine by cultured rat and human colon.

A model system for comparing carcinogen metabolism between human and rat colon has been developed. Tissue explants maintained under chemically defined conditions were treated with radioactively labeled carcinogens. After incubation for 24 hours, the binding of radioactive carcinogen to DNA was quantitated. Further, the carcinogen-DNA adducts and carcinogen metabolites released into the culture media were identified. Both human and rat colon activate benzo[a]pyrene (BP), aflatoxin B1 (AFB), and 1,2-dimethylhydrazine (DMH) into chemical species that reacted with cellular macromolecules. When human and rat colons were compared, the metabolism of AFB and DMH was qualitatively similar - the same major carcinogen-DNA adducts and metabolic profile. However, the mean binding levels of DMH and AFB to colonic DNA were higher in rats than in humans. BP-guanine adducts were the major adducts formed by both rat and human colonic DNA. However, BP-adenine adducts were observed in rat colonic DNA but not in human colonic DNA. A positive correlation for the binding of BP and DMH to human DNA of different individuals was observed, but no correlation was found between BP and AFB. The data suggest that similar enzyme systems may be involved in the metabolism of BP and DMH, whereas different enzymes might be involved in the metabolic activation of AFB.

1,2-Dimethylhydrazine↗
PubMed1980

Putrescine stimulates growth of human bronchial epithelial cells in primary culture.

Explants of adult human bronchus were cultured in CMRL-1066 medium supplemented with heat-inactivated fetal bovine serum, hormones, antibiotics, and either 0.0, 0.1, 1, or 10 mM putrescine. The outgrowth of bronchial epithelial cells was stimulated in medium containing 1 mM putrescine, a concentration that partially inhibited the outgrowth of fibroblasts. In medium containing 10 mM putrescine, the outgrowth of epithelial cells was similar to that observed in the control medium, but the outgrowth of fibroblasts was completely inhibited for periods of at least 4 weeks. When 10 mM putrescine was added to cultures of bronchial fibroblasts, the fibroblasts were not killed. These results suggest that human bronchial epithelial cells have a higher requirement for putrescine for growth than fibroblasts, and the molecular basis for this observation is under investigation.

Bronchi↗
PubMed1980

Induction of atypical squamous metaplasia with benzo[a]pyrene in cultured hamster tracheas.

Areas of hyperplasia were produced in hamster tracheal epithelium maintained in vitro by exposure to a suspension of benzo[a]pyrene (BP) in gelatin. Typical and atypical epiodermoid metaplasia were seen by 2 weeks. In atypical areas, cell nuclei were enlarged with prominent nucleoli, the cytoplasm contained dense bundles of tonofilaments and the cells were joined by numerous desmosomes. The peak response to the carcinogen was reached 4 weeks after the application of BP and consisted of extensive atypical epidermoid metaplasia. Tracheas treated with gelatin alone maintained a columnar epithelium for 6 weeks of culture. The characteristics of the metaplastic changes in vitro are essentially identical to those described after exposure of the hamster tracheobronchial epithelium to benzo[a]pyrene-ferric oxide in vivo.

Animals↗
PubMed1980

Metabolism of 1,2-dimethylhydrazine by cultured human colon.

The overall metabolism of 1,2-dimethylhydrazine, and organotropic colon carcinogen in rodents, has been studied using human colon explant cultures. The binding level of 1,2-dimethylhydrazine to DNA which in this study includes both reaction of metabolites with DNA and incorporation of radioactive metabolites into DNA, showed a 100-fold variation among the 120 people studied. When different anatomical colonic sites were compared, the highest mean binding levels were found in the ascending and sigmoid colon. No significant difference in the median and mean binding levels were observed in nontumorous colon obtained surgically from patients with colon cancer and colon obtained from immediate autopsy, but decreased mean binding levels were seen in tissues obtained by surgery from patients with non-cancerous colonic disorders. Several exogenous chemicals were found to modify the metabolism. When the colon explants were co-incubated with 1,2-dimethylhydrazine and these chemicals, the binding level of 1,2-dimethylhydrazine to DNA was (a) increased by either indole 3-carbinol or phenobarbital, (b) decreased with disulfiram, butylated hydroxytoluene, or taurodeoxycholic acid, and (c) unaltered by lithocholic acid.

1,2-Dimethylhydrazine↗
PubMed1980

Ultrasensitive enzymatic radioimmunoassay (USERIA) detects femtomoles of acetylaminofluorene-DNA adducts.

USERIA is a modification of radioimmunoassay and enzyme-liked immunosorbent assay. When compared to these assays, USERIA is 60- and 10-fold, respectively, more sensitive for the detection of adducts in DNA modified by the chemical carcinogen, 2-acetylaminofluorene (AAF). The specific antigen-antibody reaction is enzymatically amplified by an anti-IgG alkaline phosphatase conjugate which converts the substrate, [3H]adenosine-5'-monophosphate, to [3H]adenosine. As few as 2 fmol of AAF-DNA adducts can be detected by a competitive USERIA assay and less than 3 fmol of the specific adduct, N-(deoxyguanosine-8-yl)-AAF, can be detected using a non-competitive USERIA approach. The sensitivity of USERIA should aid efforts to measure carcinogen-DNA adducts in biological specimen samples from humans and experimental animals.

2-Acetylaminofluorene↗
PubMed1980

Individual differences in cancer susceptibility.

The major determinants of cancer risk are environmental carcinogens and predisposing host factors. Interactions between these determinants are now being studied by clinical-laboratory investigations. An individual may be predisposed to cancer by both genetic and acquired conditions. Genes related to malignancy and to carcinogenesis have been mapped to individual chromosomes in several species, including humans. Because most environmental chemical carcinogens require enzymatic activitation and a wide variation in carcinogen metabolism among people has been found, the ratio of metabolic activation to deactivation of carcinogens may ascertain, in part, a person's cancer risk. Additionally, cancer risk of chemical and physical agents can be qualitatively predicted by carcinogenicity tests in experimental animals. The emerging field of cancer ecogenetics is aiding efforts to prevent human cancer.

Animals↗
PubMed1979

Relationship between sister chromatid exchange and mutagenicity, toxicity and DNA damage.

Reciprocal exchanges of DNA in sister chromatids (SCEs) are induced by various carcinogens and mutagens, although the quantitative relationship between the number of mutations and SCEs induced varies among chemicals. Nevertheless, the analysis of SCE production by various agents is often proposed as a sensitive and quantitative assay for genetic damage of the sort leading to mutation and cancer. In V-79 Chinese hamster cells we have been measuring DNA damage by alkaline elution, mutation induction as detected by 6-thioguanine resistance, and cytotoxicity as detected by colony formation for different physical and chemical agents. Some of the agents produced varying forms of DNA damage but undetectable increases in either mutation or toxicity. We report here that some undetectably mutagenic and/or toxic agents produce increases in SCE frequency and that DNA single-stranded breaks, DNA--DNA interstrand cross-links, and DNA--protein cross-links are not necessary for SCE.

Animals↗
PubMed1979

A comparison of cytotoxicity, ouabain-resistant mutation, sister-chromatid exchanges, and nascent DNA synthesis in Chinese hamster cells treated with dihydrodiol epoxide derivatives of benzo[a]pyrene.

Chinese hamster V79 cells were treated with either (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P-diol epoxide I) or (+/-)-7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P-diol epoxide II) and the nascent DNA was labeled with [Me-3H]thymidine. The cells were harvested for determination of cytotoxicity, sister-chromatid exchanges (SCE), ouabain-resistant (Or) mutations and the size of newly synthesized daughter-strand DNA. Both isomers caused dose-dependent decreases in survival of cells and in the size of nascent DNA. Increases in the frequencies of SCE and of Or mutation were found in cells treated with either isomer. However, B[a]P-diol epoxide I caused 10--20-fold more Or mutations and 50-100% more SCE than did B[a]P-diol epoxide II at equal molar dose levels. In contrast to the marked difference in the frequencies of both SCE and Or mutations caused by both compounds, the isomers induced similar reductions in the size of the nascent DNA at equal dose levels. In comparing the molecular and biological effects of the two isomers the reduction in the size of nascent DNA was more closely related to cytotoxicity than to the induction of SCE or Or mutations.

Animals↗
PubMed1979

The effect of caffeine on cytotoxicity, mutagenesis, and sister-chromatid exchanges in Chinese hamster cells treated with dihydrodiol epoxide derivatives of benzo[a]pyrene.

The effect of caffeine on Chinese hamster V79 cells after treatment with the highly mutagenic (+/-)-7 beta,8 alpha-dihydroxy-9 alpha, 10 alpha-7,8,9,10-tetrahydrobenzo[a]pyrene, and the weaker mutagen (+/-)-7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, B[a]P-deiol-epoxide II, was studied at both the biological and molecular levels. Caffeine, at nontoxic dose levels, caused a synergistic reduction in cell survival induced by both isomers and also inhibited DNA elongation as measured by alkaline sucrose-gradient analysis of nascent DNA. However, caffeine did not affect the induction of either ouabain-resistant mutants or sister-chromatid exchanges by either isomer. These results suggest that enhanced cell killing by caffeine in benzo[a]pyrene-diol-epoxide treated V79 cells may be related to caffeine's inhibitory effect on DNA elongation. However, inhibition of DNA elongation by caffeine did not influence the resulting induced levels of mutagenesis or sister-chromatid exchanges.

Animals↗
PubMed1979

Ultrasensitive enzymatic radioimmunoassay: application to detection of cholera toxin and rotavirus.

Rotavirus and enterotoxin-producing bacteria are major causes of diarrheal disease in humans. A method of rapid diagnosis, ultrasensitive enzymatic radioimmunoassay, has been developed to quantitatively detect cholera toxin and rotavirus. The method uses features of both enzyme-linked immunosorbent assay and radioimmunoassay; however, the sensitivity of the assay is 100- to 1000-fold more sensitive than the two parent assays. Ultrasensitive enzymatic radioimmunoassay should also be useful in measuring other biologically important agents such as drugs and hormones.

Alkaline Phosphatase↗
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↗