Additional evidence for the involvement of the 3,4-diol 1,2-oxides in the metabolic activation of 7,12-dimethylbenz[a]anthracene in mouse skin

Cooper, Christopher S.; Ribeiro, O.; Hewer, Alan; Walsh, C.; Grover, Philip L.; Sims, P.

doi:10.1016/0009-2797(80)90154-4

Cited by 25 publications

(12 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the elution profiles obtained in this study (Fig. 26) for the 3 groups of rat cells are also identical and in agreement with those reported for the major DMBA-nucleic acid adducts found in mouse skin (285,286), rodent embryo cells in culture (287)(288)(289)(290), and human mammary epithelial cells (293) treated with DMBA. On the basis of these comparisons, peaks I, II, and III (for YV), A, B, and C (for P) and X, Y, and Z (for OV) (Fig.…”

Section: Mammary Gland Carcinogenesissupporting

confidence: 90%

“…Much of the evidence on the nature of the DMBAnucleic acid adducts is derived from studies which determine the photosensitivity and fluorescence properties of the adduct after separation by Sephadex LH-20 column chromatography. Using the chromatographic method developed by Baird and Brookes (284), DMBA-DNA adduct peaks have been obtained following chromatography on Sephadex LH-20 columns of DNA hydrolysates prepared from mouse skin (285,286) or rodent embryo cells (287)(288)(289)(290), or from DNA incubated with DMBA in vitro in the presence of a hamster liver microsomal system (289). Fluorescence studies by Vigny et al (286) also indicate that the adduct peaks possess anthracene-like properties, while studies by Baird and co-workers (291,292) demonstrate that the adducts are photosensitive, a property seen also with 9,10-dimethylbenz(a)anthracene.…”

Section: Mammary Gland Carcinogenesismentioning

confidence: 99%

See 1 more Smart Citation

Differentiation of the mammary gland and susceptibility to carcinogenesis

Russo¹,

Tay²,

Russo³

1982

Breast Cancer Res Tr

562

402

View full text Add to dashboard Cite

It has been demonstrated that in humans certain factors such as early menarche, late pregnancy, and nulliparity are associated with a higher risk of developing breast cancer, while early pregnancy acts as a protective factor. Induction of mammary cancer in rats by administration of the chemical carcinogen 7,12-dimethylbenz(a)anthracene reveals that the same factors influencing human breast cancer risk also affect the susceptibility of the rat mammary gland to the chemical carcinogen. Nulliparous rats and rats undergoing pregnancy interruption are more susceptible to developing carcinomas. This fact has been attributed to the incomplete differentiation of the gland at the time of carcinogen administration. Parous rats are resistant to the carcinogenic effect of DMBA, which is explained by the complete development of the gland attained during pregnancy and lactation. This development is manifested by the differentiation of terminal end buds into secretory units, which have a smaller proliferative compartment; the epithelial cells of these secretory units have a longer cell cycle, less avidity for binding DMBA, and possess a more efficient DNA excision repair capacity.

show abstract

Section: Mammary Gland Carcinogenesissupporting

confidence: 90%

Section: Mammary Gland Carcinogenesismentioning

confidence: 99%

Differentiation of the mammary gland and susceptibility to carcinogenesis

Russo¹,

Tay²,

Russo³

1982

Breast Cancer Res Tr

562

402

View full text Add to dashboard Cite

show abstract

“…11). These results are in agreement with those reported for the major DMBAnucleic acid adducts generated in mouse skin (142), rodent embryo cells in culture (143,144) and in human mammary epithelial cells (145) treated with DMBA. Although our results are consistent with the bay-region theory of polycyclic hydrocarbon carcinogenesis (146) and provide evidence that …”

Section: Dmba-dna Binding By Rat Mammary Epitheliumsupporting

confidence: 83%

Molecular and Cellular Basis of the Mammary Gland Susceptibility to Carcinogenesis

Russo¹,

Tay²,

Ciocca³

et al. 1983

Environmental Health Perspectives

View full text Add to dashboard Cite

Mammary carcinomas induced by the administration of 7,12-dimethylbenz(a)anthracene (DMBA) to young virgin rats arise from undifferentiated terminal ductal structures called terminal end buds (TEBs). TEBs that normally differentiate into alveolar buds (ABs) and lobules under the influence of DMBA develop intraductal proliferations which progress to carcinoma. The high susceptibility of the young virgin rat TEBs to neoplastic transformation is due to its large proliferative compartment, with cells cycling every 10 hr, and to a higher 3H-DMBA uptake. Progressive differentiation of TEBs into ABs and lobules or their regression to terminal ducts (TDs) is seen with aging. Complete differentiation of the gland is attained only through pregnancy and lactation. The greater differentiation of the gland is manifested as permanent structural changes, consisting in the disappearance of TEBs and in a diminution of the number of TDs due to their differentiation into ABs and lobules. This greater differentiation results in a diminished or total refractoriness of the gland to the carcinogen because ABs and lobules have a lower proliferative compartment and a longer cell cycle than TEBs and TDs. Cells of parous rats have both in vivo and in vitro a lower DMBA-DNA binding capacity, a lower DNA synthesis and a greater ability to repair DMBA damaged DNA than cells of young virgin rats. The more efficient DNA repair capacity of the parous rat mammary gland is demonstrated by the induction of unscheduled DNA synthesis and a removal of DMBA-DNA adducts.

show abstract

“…Truns-l,2-Dihydro-l,2-dihydroxybenz(a)anthracene (BA 1 ,2-diol), trans-3 ,4-dihydro-3 ,4-dihydroxybenz(a)anthracene (BA 3,4-diol), trans-l0,11dihydro-l0,ll-dihydroxybenz(a)anthracene (BA 10, 11-diol), trans-3,4-dihydro-3,4-dihydroxy-7,12-dimethylbenz(u)anthracene (DMBA 3,4-diol), truns-5,6dihydro-S,6-dihydroxy-7,12-dimethylbenz(a)anthra-cene (DMBA 5,6-diol), trans-8,9-dihydro-8,9-dihydroxy-7,22-dimethylbenz(a)anthracene (DMBA 8,9diol) and trans-l0,1 I-dihydro-l0,11 -dihydroxy-7,12dimethylbenz(a)anthracene (DMBA 10, were prepared from the parent hydrocarbons by oxidation using an ascorbic acid:ferrous su1phate:ED-TA system as described (Tierney et al, 1978). tram-5,6-Dihydro-5,6-dihydroxybenz(a)anthracene (BA 5, (Boyland and Sims, 1964), irans-8,9-dihyd-ro-8,9-dihydroxybenz(a)anthracene (BA 8, (Lehr et al, 1977a), trans-4,5-dihydro-4,5-dihydroxybenzo(a)pyrene (BP 4,5-diol) (Sims, 1970), trans-7,8-dihydro-7,8-dihydroxybenzo(a)pyrene (BP 7,8-diol) (McCaustland and Engel, 1975), trans-9,10-dihydro-9,10-dihydroxybenzo(a)pyrene (BP 9,lO-diol) (McCaustland et al, 1976b), r-7, t-8-dihydroxy-2-9 ,lO-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (anti-BP-7,8-diol 9,lO-oxide) (Mc Caustland et al, 1976a) and r-8,t-9-dihydroxy-t-lO,l1-oxy-8,9,10,1l-tetrahydrobenz(a)anthracene (anti-BA-8,9-diol l0,ll-oxide) (Lehr et al, 19776) were prepared by synthesis and t-3,r-4-dihydroxy-t-l,2-0~~-1,2,3,4-tetrahydro-7,12-dimethylbenz(a)anthracene (anti-DMBA-3,4-diol 1,2-0xide) was prepared by oxidizing the related dihydrodiol with mchloroperoxybenzoic acid as described (Cooper et al, 1980b).…”

Section: Methodsmentioning

confidence: 99%

Polycyclic hydrocarbon activation and metabolism in epithelial cell aggregates prepared from human mammary tissue

Grover

MacNicoll

Sims

et al. 1980

Intl Journal of Cancer

View full text Add to dashboard Cite

The metabolism of benz(a)anthracene (BA), 7,12-dimethylbenz(a)anthracene (DMBA) and benzo(a)pyrene (BP) by human mammary epithelial cell aggregates in culture has been investigated using non-neoplastic tissues obtained from eight patients undergoing reduction mammoplasty. All three hydrocarbons were metabolized to water-soluble and organic solvent-soluble products and the latter included both K-region and non-K-region dihydrodiols. The major dihydrodiols detected as metabolites of the parent hydrocarbons were the 8,9-dihydrodiols of BA and DMBA and the 9,10-dihydrodiol of BP. The 1,2-dihydrodiols of BA and DMBA and the 11,12-dihydrodiol of BP were not detected. The hydrocarbons also became bound to the proteins and DNA of the epithelial cells but there were wide differences in the extents of binding occurring with the different hydrocarbons and in the extents of metabolism and binding occurring with tissue preparations from different patients. Some of the hydrocarbon-deoxyribonucleoside adducts formed from DMBA and BP appeared to have arisen through reactions of "bay-region" diol-epoxides with DNA, but only very low levels of reaction with DNA were detected in tissue preparations treated with BA.

show abstract

Additional evidence for the involvement of the 3,4-diol 1,2-oxides in the metabolic activation of 7,12-dimethylbenz[a]anthracene in mouse skin

Cited by 25 publications

References 30 publications

Differentiation of the mammary gland and susceptibility to carcinogenesis

Differentiation of the mammary gland and susceptibility to carcinogenesis

Molecular and Cellular Basis of the Mammary Gland Susceptibility to Carcinogenesis

Polycyclic hydrocarbon activation and metabolism in epithelial cell aggregates prepared from human mammary tissue

Contact Info

Product

Resources

About