<i>In Vitro</i>
            Transformation of Rodent Cells by K-Region Derivatives of Polycyclic Hydrocarbons

Grover, Philip L.; Sims, P.; Huberman, Eliezer; Marquardt, Hans; Kuroki, Toshio; Heidelberger, Charles

doi:10.1073/pnas.68.6.1098

Cited by 152 publications

(60 citation statements)

References 32 publications

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“…The capacity of lung cells to induce microsomal enzymes would seem to be advantageous in view of reports that prior administration of AHH-inducing agents to laboratory animals prevented tumorigenesis by BP (19) and induced AHH levels lead to rapid conversion to noncarcinogenic metabolites, then either inhibition or induction of the enzyme results in lower rates of tumor formation (14,(19)(20)(21).…”

Section: Resultsmentioning

confidence: 99%

“…Liver and lung contain large amounts, while lesser amounts are found in the intestine, thyroid, adrenal, testis, muscle, placenta, skin, and leuko- cytes (5)(6)(7)(8)(9)(10)(11)(12)(13). A function of this enzyme system is to transform carcinogenic polycyclic hydrocarbons such as 3,4-BP or 3-methylcholanthrene (MC) to metabolites with altered carcinogenic properties (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Induction of Aryl Hydrocarbon Hydroxylase in Human Pulmonary Alveolar Macrophages by Cigarette Smoking

Cantrell¹,

Warr²,

Busbee³

et al. 1973

J. Clin. Invest.

142

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Induction of Aryl Hydrocarbon Hydroxylase in Human Pulmonary Alveolar Macrophages by Cigarette Smoking

Cantrell¹,

Warr²,

Busbee³

et al. 1973

J. Clin. Invest.

142

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“…The postulated mechanisms for a possible increased risk of chemical carcinogenesis in cigarette smokers with high levels of AHH concern the production during metabolism and/or remetabolism of the polycyclic aromatic hydrocarbons in cigarette smoke to intermediate products of high mutagenic (6)(7)(8)(9)(10) and carcinogenic (11)(12) potential. In addition to differences in the generation of metabolites, another critical factor in determining susceptibility to carcinogens might be individual variation in the affinity of binding of these metabolites to DNA (24).…”

Section: Methodsmentioning

confidence: 99%

“…benzo(a)pyrene and benzo(a)-anthracene [BA]) into more polar, water-soluble compounds that are eliminated from the body. During hydroxylation, intermediate compounds with enhanced mutagenic (6)(7)(8)(9)(10) and carcinogenic (11,12) activities are formed. Large quantities of AHH may be harmful to cigarette smokers through increased production of these potent intermediate compounds from the polycyclic hydrocarbons present in cigarette smoke.…”

mentioning

confidence: 99%

Comparison of Aryl Hydrocarbon Hydroxylase Induction in Cultured Blood Lymphocytes and Pulmonary Macrophages

McLemore¹,

Martin²,

Toppell³

et al. 1977

J. Clin. Invest.

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A B S T R A C T Aryl hydrocarbon hydroxylase induction was studied in cultured peripheral blood lymphocytes and pulmonary alveolar macrophages from 15 smokers and 8 nonsmokers with a variety of pulmonary diseases. Enzyme levels in lymphocytes from cigarette smokers cultured in medium without an inducing agent were 57±6 mU/106 cells (mean+SEM), while enzyme levels in lymphocytes from nonsmokers were 20+2 mU/106 cells (P < 0.001). When lymphocytes were cultured in the presence of the inducing agent, benzo-(a)anthracene, enzyme activity was increased to 168 +23 mU/106 cells in smokers' cells and 99+22 mU/106 cells in lymphocytes from nonsmokers (P < 0.04).When noninduced enzyme values in cultured macrophages were compared, smokers' cells had enzyme levels of 45+5 mU/106 cells, whereas nonsmokers had enzyme activity of 24±2 mU/106 cells (P < 0.002). However, pulmonary macrophages from smokers or nonsmokers, cultured in the presence of benzo(a)-anthracene, had similar levels of induced enzyme activity (P > 0.1). A positive correlation was observed for nonsmokers (r = 0.596, P > 0.1 <0.2) or smokers (r = 0.640, P < 0.04), when enzyme values for noninduced cultures of macrophages and lymphocytes from individual patients were simultaneously compared. Enzyme values for macrophages and lymphocytes cultured in the presence of an inducer also revealed a positive correlation for individual smokers (r = 0.801, P < 0.001) or nonsmokers (r = 0.785, P < 0.01). Inducibility (expressed as fold-induction) for macrophages Dr positively correlated (r = 0.889, P < 0.001 for nonsmokers and r = 0.942, P < 0.001 for smokers). These results indicate that the capacity for aryl hydrocarbon hydroxylase induction is similar whether tested in lymphocytes or pulmonary macrophages from this group of pulmoniary disease patients.

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“…They are also toxic and mutagenic, and have been shown to transform rodent cells in in vitro culture (Grover et al, 1971). This mutagenicity is stated to correlate with the degree of carcinogenicity of the parent hydrocarbons.…”

mentioning

confidence: 99%

Biological Activity and Electronic Structure of the Aflatoxins

Heathcote¹,

Hibbert²

1974

Br J Cancer

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Summary.-In theoretical studies of aromatic hydrocarbons, Pullman and Pullman (1969) used the molecular orbital method to correlate electronic structure with biological activity. They suggested that the interaction between carcinogens and their molecular receptors must occur through the K region of the carcinogenic molecule and involve a strong chemical binding of the type of an addition reaction.In the present work the electronic structures of aflatoxins B1, G1, 4-20 dehydro B1 and of versicolorin A have been determined by the simple Huckel molecular orbital method using a computer, in order to see whether thU correlation between electronic structure and biological activity is applicable to these compounds also. Calculations show that the 2-3 pi-bond, which has the highest bond order of the aflatoxin molecules, should be the most susceptible to electrophilic attack and is the most probable location of the K region. This is in agreement with the experimental observation of Dutton and Heathcote (1968) that aflatoxins B1 and G1 hydrate rapidly in dilute acid to the hydroxyaflatoxins B2a and G2a with an apparent total loss of carcinogenicity. The calculations also show that aflatoxins B1 G1 and M1 have no suitable site for an L region and this probably accounts for their highly carcinogenic nature.

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In Vitro Transformation of Rodent Cells by K-Region Derivatives of Polycyclic Hydrocarbons

Cited by 152 publications

References 32 publications

Induction of Aryl Hydrocarbon Hydroxylase in Human Pulmonary Alveolar Macrophages by Cigarette Smoking

Induction of Aryl Hydrocarbon Hydroxylase in Human Pulmonary Alveolar Macrophages by Cigarette Smoking

Comparison of Aryl Hydrocarbon Hydroxylase Induction in Cultured Blood Lymphocytes and Pulmonary Macrophages

Biological Activity and Electronic Structure of the Aflatoxins

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