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E Huberman

Publications and source records attributed to E Huberman.

157 records · Page 9Linked to original sources
PubMed1971

Mutagenicity to mammalian cells of epoxides and other derivatives of polycyclic hydrocarbons.

The cytotoxicity and mutagenicity of several polycyclic hydrocarbons and their K-region derivatives were tested in a clone of Chinese hamster cells; the production of clones resistant to 8-azaguanine was used as the marker for mutagenesis. In the series related to benz(a)anthracene, the K-region epoxide was highly mutagenic, and the phenol was less mutagenic; the hydrocarbon and cis and trans-dihydrodiols were not mutagenic. Seven resistant clones were isolated and retained their drug-resistance; three of these could be reverted to the wild type. There was no difference in the chromosome numbers among the parent and mutant clones. The results in the methylcholanthrene series were similar to those for benz(a)anthracene. However, in the dibenz(a,h)anthracene series, the phenol was more mutagenic than the epoxide. 7-Methylbenz(a)anthracene epoxide and 7-bromomethylbenz(a)anthracene were highly mutagenic, 7-bromomethyl-12-methylbenz(a)anthracene was less mutagenic, and the parent hydrocarbons were inactive. These results demonstrate that metabolic activation of polycyclic hydrocarbon is required for mutagenic activity in mammalian cells.

Animals↗
PubMed1971

In vitro transformation of rodent cells by K-region derivatives of polycyclic hydrocarbons.

The K-region epoxides and cis-dihydrodiols derived from benz(a)anthracene and from dibenz(a,h)-anthracene have been found to be more active in the production of malignant transformation in hamster embryo cells than the hydrocarbons or the corresponding K-region phenols. The K-region epoxides derived from benz(a)-anthracene and from 3-methylcholanthrene were also active in transforming a clone of ventral prostate cells from the C3H mouse that was not readily transformed by the parent hydrocarbons. The phenols were the most toxic compounds tested but did not transform cells; this confirms that toxicity and transformation are not directly related events. The results obtained support the view that metabolism of polycyclic hydrocarbons precedes toxicity and transformation in rodent cells in culture.

Animals↗
PubMed1969

Enzymatic hydroxylation of benzopyrene and its relationship to cytotoxicity.

Aryl hydrocarbon hydroxylase, an inducible microsomal enzyme system, has been measured in cultures of normal and transformed hamster, mouse, and human cells. In order to determine the highest level of enzyme, the cells were induced by pretreatment with benz(a)anthracene. A correlation was found between the level of enzyme activity and the susceptibility of the cells to the cytotoxicity produced after treatment with benzopyrene. The results indicate that aryl hydrocarbon hydroxylase is the enzyme system responsible for cell susceptibility to the cytotoxic effect of benzopyrene and the toxic effect of benzopyrene is due to its enzymatic conversion to a cytotoxic metabolite. 3-Hydroxybenzopyrene, one of the products of the enzymatic hydroxylation of benzopyrene, was found to be cytotoxic to cells that were either susceptible or resistant to the cytotoxic effect of benzopyrene.

Animals↗
PubMedDate not supplied

Mutagenesis and cell transformation of mammalian cells in culture by chemical carcinogens.

In the process of in vitro cell transformation, normal cells, which have an oriented pattern of growth and a limited life span in vitro and which are not tumorigenic, are converted into cells that have a hereditary random pattern of growth, the ability to grow continuously in culture, and the ability to form tumors. Such heritable phenotypic changes may arise from alterations in gene expression due to somatic mutations after interaction of the carcinogen with due to somatic mutations after interaction of the carcinogen with cellular DNA. Our studies have indeed shown (a) that metabolically activated carcinogenic polycyclic hydrocarbons which have been shown to bind to cellular DNA induce somatic mutations in mammalian cells; (b) that there is a relationship between the degree of mutant induction and the degree of carcinogenicity of the different hydrocarbons tested; and (c) that the somatic mutations were induced by metabolites rather than by the hydrocarbons themselves. In the case of benzo(a)pyrene (BP), a very common carcinogenic polycyclic hydrocarbon, its 7,8-diol-9,10-oxide was identified as the major mutagenic and cell-transforming metabolite. Based on these studied, it was possible to estimate the genetic target size for cell transformation by comparing in the same cells the frequency of cell transformation and mutation for ouabain resistance (which is presumably due to a mutation at one locus) induced BP and by one of its major metabolites. The results indicated that the target size for transformation is 20 times larger than that determined for ouabain resistance. This suggests that cell transformation, as determined by a hereditary pattern of cell growth, may be due to a mutation and that this mutation can occur in one out of a small number of the same or different genes.

Animals↗