The Bay-Region Theory of Carcinogenesis by Polycyclic Aromatic Hydrocarbons

Jerina, Donald M.; Yagi, H.; Lehr, Roland E.; Thakker, Dhiren R.; Schaefer-Ridder, Maria; Karle, Jean M.; Levin, Wayne; Wood, Alexander W.; Chang, Richard L.; Conney, Allan H.

doi:10.1016/b978-0-12-279201-4.50015-3

Cited by 43 publications

(44 citation statements)

References 41 publications

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“…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: 81%

Molecular and Cellular Basis of the Mammary Gland Susceptibility to Carcinogenesis

Russo¹,

Tay²,

Ciocca³

et al. 1983

Environmental Health Perspectives

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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.

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Section: Dmba-dna Binding By Rat Mammary Epitheliumsupporting

confidence: 81%

Molecular and Cellular Basis of the Mammary Gland Susceptibility to Carcinogenesis

Russo¹,

Tay²,

Ciocca³

et al. 1983

Environmental Health Perspectives

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show abstract

“…The mass spectrum ffig3c) of the methanolysed product revealed that the methoxyl group was introduced to C4 of the epoxide. This is again consistent with the theoretical prediction [9] that the benzylic position at C4 would be more reactive than Cg. Theoretical calculations also indicated that the bay-region diol-epoxide (I) should be more reactive than the non bay-region 1,2dihydrodiol-3,4-epoxide.…”

Section: Elsevierlnorth-holland Biomedical Presssupporting

confidence: 81%

Solvolysis of the bay‐region diol‐epoxide of benz[a]anthracene

Wu¹,

Wong²

1980

FEBS Letters

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“…Further stereoselective reactions of the dihydrodiols and phenols with cytochrome P-450 can lead to secondary metabolites such as diol epoxides and epoxyphenols. The most important secondary metabolite is the anti-7,8-diol-9,10-epoxide, which is a major ultimate carcinogenic form of BaP (40,41). The free-radical or one-electron oxidation pathway involves the enzymatic formation of 6-hydroxy-BaP via a direct oxygen insertion mediated by cytochrome-P-450, or possibly via the reaction of the enzymatically formed BaP cation radical with water.…”

Section: Oxygenated Bap Radicalsmentioning

confidence: 99%