Differential Toxicity Response of Normal and Neoplastic Cells In Vitro to 3,4-Benzopyrene and 3-Methylcholanthrene

Alfred, Lawrence J.; Globerson, Amiela; Berwald, Yoheved; Prehn, Richmond T.

doi:10.1038/bjc.1964.18

Cited by 34 publications

(11 citation statements)

References 3 publications

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“…These compounds undergo various metabolic transformations in vivo (see review in Boyland and Weigert, 1947; Miller and Miller, 1965). In vitro they are rapidly accumulated by normal and neoplastic cells (Marimura, Kotin and Falk, 1964;Alfred et al, 1964;Diamond, 1966). It was not known, however, whether these substances might be metabolized by cells growing in vitro.…”

mentioning

confidence: 99%

Metabolic degradation of 3,4-benzopyrene in the cultures of normal and neoplastic fibroblasts.

Andrianov¹,

Belitsky²,

Ivanova³

et al. 1967

Br J Cancer

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DIFFERENTIAL sensitivity of normal and neoplastic rodent fibroblasts growing in vitro to the toxic action of carcinogenic polycyclic hydrocarbons, suggested long ago by Haddow (1938), has been demonstrated by a number of investigators (Starikova and Vasiliev, 1962;Berwald and Sachs, 1963; Alfred and collaborators, 1964;Diamond, 1966). Neoplastic cells were found to be much more resistant to these compounds than their normal counterparts. Resistance to the toxic effects of carcinogenic hydrocarbons was shown to be characteristic for the cells of sarcomas induced by various types of agents: carcinogenic chemicals, plastic films, SV40 and polyoma viruses. Thus, decrease of the sensitivity to carcinogens regularly accompanied neoplastic transformation of these cells (see review and discussion in Vasiliev and Guelstein, 1963Guelstein, , 1966.The causes of the differential sensitivity of normal and neoplastic cells to carcinogenic hydrocarbons remain obscure. These compounds undergo various metabolic transformations in vivo (see review in Boyland and Weigert, 1947; Miller and Miller, 1965). In vitro they are rapidly accumulated by normal and neoplastic cells (Marimura, Kotin and Falk, 1964;Alfred et al., 1964;Diamond, 1966). It was not known, however, whether these substances might be metabolized by cells growing in vitro.The experiments described in this paper were performed in order to study the rate of metabolism of a carcinogenic hydrocarbon, 3,4-benzopyrene (BP), in cultures of normal and neoplastic fibroblasts of mice and hamsters.Similar experiments were made with cultures of fibroblasts from normal human embryos. As shown by Diamond (1966) and confirmed in this laboratory, normal human fibroblasts, in contrast to normal rodent cells, are resistant to the toxic effects of carcinogenic hydrocarbons. MATERIALS AND METHODS Cell culturesFirst subcultures of trypsinized cells of mouse, hamster and human embryos were used; the age of human embryos taken for trypsinization was about 2-3 months, that of rodent embryos about 17-19 days of pregnancy.Trypsinized embryonic cells were first grown in large vessels and then transferred into stoppered Carrel flasks 5 cm. in diameter. Continuous lines of neoplastic cells were also grown in Carrel flasks. Some information on the origin

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mentioning

confidence: 99%

Metabolic degradation of 3,4-benzopyrene in the cultures of normal and neoplastic fibroblasts.

Andrianov¹,

Belitsky²,

Ivanova³

et al. 1967

Br J Cancer

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“…The results recorded in Table II demonstrate that the specific fluorescence material disappeared from the medium after 24 hours, but this material could not be detected by fluorescence in the total cell digests. However, sub- (Alfred, Globerson, Berwald and Prehn, 1964). It should be noted that the cell number and cell size of the two types of cultures were same at the time of carcinogen application.…”

Section: Resultsmentioning

confidence: 96%

“…complete medium or 62-5 /UM. Previous experiments (Alfred, Globerson, Berwald and Prehn, 1964) indicated that normal embryo cell cultures, exposed to paraffin impregnated discs of 3,4-benzopyrene particles, produced greater amounts of total protein per cell than untreated controls. The question whether soluble 3,4-BP complexes would similarly " stimulate " an increase in protein synthesis in the same cell system was analyzed.…”

Section: Resultsmentioning

confidence: 97%

“…A cytotoxicity response of normal embryo cells in culture to certain hydrocarbon carcinogens in colloidal suspension (Alfred, Globerson, Berwald and Prehn, 1964) might represent one manifestation of the initial reaction between cell and chemical carcinogen. However, it was not possible by this or other methods (Starikova and Vasiliev, 1963) to analyze quantitatively the various parameters associated with the cell-carcinogen interaction.…”

Section: Interaction Of Soluble Complexes Ofmentioning

confidence: 99%

“…The cell culture methods used in the present study were described previously (Alfred, Globerson, Berwald and Prehn, 1964). Secondary monolayer cultures were prepared from cells, which originally were derived from normal embryos of C3H or C57B1 mice, and from 3,4-benzopyrene induced sarcomas (C7 tumour) produced by a single subcutaneous injection of 0-1 ml.…”

Section: Cell Culturesmentioning

confidence: 99%

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Interaction of Soluble Complexes of Tritiated 3,4-Benzopyrene and Animal Cells In Vitro

Lj¹

1964

Br J Cancer

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THERE are several probable sites at which a carcinogenic hydrocarbon may interact with a susceptible animal cell, triggering the process of neoplastic transformation: (1) a direct interaction with the genetic material (DNA), resulting in somatic mutation. So far, however, no direct evidence has been presented for this possible reaction, (2) interactions with cytoplasmic components which might result in a neoplastic state which is not based on structural change at the DNA level. Recent evidence has been presented by Heidelberger and Davenport (1961) and Abell and Heidelberger (1962) (Starikova and Vasiliev, 1963) to analyze quantitatively the various parameters associated with the cell-carcinogen interaction. The insolubility in aqueous solution of these hydrocarbons has thus far prevented their incorporation into physiologically compatible culture medium.The finding that low concentrations of polycyclic hydrocarbons are solubilized by aqueous purine solutions (Weil-Malherbe, 1946;Boyland and Green, 1962) stimulated further study in this laboratory on the interactions in vitro between animal cells and carcinogenic hydrocarbons. Experiments were designed to follow the possible site of interaction and binding capacity of soluble tritiated 3,4-benzopyrene complexed to non-toxic levels of caffeine, with normal mouse embryo cells in monolayer cultures.MATERIALS AND METHODS Cell culturesThe cell culture methods used in the present study were described previously (Alfred, Globerson, Berwald and Prehn, 1964). Secondary monolayer cultures were prepared from cells, which originally were derived from normal embryos of C3H or C57B1 mice, and from 3,4-benzopyrene induced sarcomas (C7 tumour) produced by a single subcutaneous injection of 0-1 ml. of a 0 5 per cent 3,4-

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Two spontaneously transformed cell lines derived from the same hamster embryo culture

Diamond

1967

Intl Journal of Cancer

115

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Differential Toxicity Response of Normal and Neoplastic Cells In Vitro to 3,4-Benzopyrene and 3-Methylcholanthrene

Cited by 34 publications

References 3 publications

Metabolic degradation of 3,4-benzopyrene in the cultures of normal and neoplastic fibroblasts.

Metabolic degradation of 3,4-benzopyrene in the cultures of normal and neoplastic fibroblasts.

Interaction of Soluble Complexes of Tritiated 3,4-Benzopyrene and Animal Cells In Vitro

Two spontaneously transformed cell lines derived from the same hamster embryo culture

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