Correlation between sensitivity to tumor promotion and sustained epidermal hyperplasia of mice and rats treated with 12-O-tetradecanoylphorbol-13-acetate

Sisskin, Enid E.; Gray, Thomas E.; Barrett, J. Carl

doi:10.1093/carcin/3.4.403

Cited by 70 publications

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“…This is further supported by the study of TPA-induced promotion in different species displaying varying hyperplasia after repeated TPA treatments, where there was generally a good correlation between the ability of TPA to promote tumours and its ability to produce a sustained epidermal hyperplasia (Sisskin & Barrett, 1981;Sisskin et al, 1982). The exception was the DBA/2 mouse strain which responded to TPA with a good sustained hyperplasia and a low tumour yield (Sisskin et al, 1982). However, this anomaly was recently shown to be due to inefficient initiation of this species by the dose of DMBA used by Sisskin and colleagues and if the correct dose of DMBA, or a different initiator such as MNNG was used, then DBA/2 mice responded to promotion by TPA with a high tumour yield (Di Giovanni et al, 1984) as predicted from their hyperplastic response (Sisskin et al, 1982).…”

Section: Two-stage Epidermal Tumourigenesismentioning

confidence: 84%

Section: Two-stage Epidermal Tumourigenesismentioning

confidence: 88%

“…The exception was the DBA/2 mouse strain which responded to TPA with a good sustained hyperplasia and a low tumour yield (Sisskin et al, 1982). However, this anomaly was recently shown to be due to inefficient initiation of this species by the dose of DMBA used by Sisskin and colleagues and if the correct dose of DMBA, or a different initiator such as MNNG was used, then DBA/2 mice responded to promotion by TPA with a high tumour yield (Di Giovanni et al, 1984) as predicted from their hyperplastic response (Sisskin et al, 1982). Furthermore, it has recently been shown that neonatal mice which are refractory to TPA-induced hyperplasia (Bertsch & Marks, 1974) are also refractory to stage I promotion by TPA (Furstenberger et al, 1985) and these refractory conditions subside in parallel as the adult pattern of epidermal differentiation appears (Furstenberger et al, 1985).…”

Section: Two-stage Epidermal Tumourigenesismentioning

confidence: 99%

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Defective responses of transformed keratinocytes to terminal differentiation stimuli. Their role in epidermal tumour promotion by phorbol esters and by deep skin wounding

Parkinson¹

1985

Br J Cancer

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Summary Epidermal tumourigenesis can be achieved in rodents by the application of a single subthreshold dose of a carcinogen (initiation) followed by repeated applications of a tumour promoter such as 12-0-tetradecanoyl phorbol, 13-acetate (TPA). TPA induces terminal differentiation in the majority of epidermal keratinocytes in vitro. However, transformed keratinocytes respond weakly to this terminal differentiation signal, and it is suggested that this property allows initiated cells and their progeny to obtain a selective advantage over their normal counterparts during promotion of papilloma formation by TPA.New data are reviewed which suggest that a putative wound hormone TGF-P has similar differential effects on normal and transformed epithelial cells to those of TPA. It is proposed that the release of TGF-,B from platelets following deep skin wounding may be an explanation as to why wounding is a promoting stimulus but milder forms of epidermal injury are not. Weakly promoting hyperplasiogenic agents are also discussed within the context of a selection theory of tumour promotion.

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Section: Two-stage Epidermal Tumourigenesismentioning

confidence: 84%

Section: Two-stage Epidermal Tumourigenesismentioning

confidence: 88%

Section: Two-stage Epidermal Tumourigenesismentioning

confidence: 99%

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Defective responses of transformed keratinocytes to terminal differentiation stimuli. Their role in epidermal tumour promotion by phorbol esters and by deep skin wounding

Parkinson¹

1985

Br J Cancer

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“…By contrast, repeated applications of a promoter in uninitiated and initiated skin produces extensive hyperplasia (Setala et al, 1959). Different strains of mice with variable sensitivity to tumor promotion by TPA exhibit a good correlation of long term tumor production with sustained hyperplasia after 4 weeks of repeated TPA treatment (Sissken et al, 1982). There is also a correlation between thickness of epidermis and tumor production in the tumor-producing range of TPA concentrations (Raick et al, 1972).…”

Section: Precancerous Pulmonary Lesions Among Smokersmentioning

confidence: 99%

Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis

Rubin

2002

Oncogene

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Historically our knowledge about the direct carcinogenic activity of cigarette smoke and its constituents grew from painting experiments on the skin of mice to produce papillomas and carcinomas. The neutral fraction of cigarette smoke condensate had most of the carcinogenic activity in this test and was rich in carcinogenic polycyclic aromatic hydrocarbons (PAHs), the most abundant by far being BP. However, the concentration of BP in the condensate was only about 2% the amount of pure BP required to cause skin tumors. In other fractions there were non-carcinogenic constituents that promoted tumor formation when applied repeatedly to mouse skin that had been initiated by a single subcarcinogenic application of BP. There were also constituents of cigarette smoke that acted as cocarcinogens when applied simultaneously with repeated applications of BP. BP was effective as an initiator at lower concentrations than as a complete carcinogen, and some non-carcinogenic PAHs in the condensate were also active initiators. It was concluded from these studies that cigarette smoke condensate is primarily a tumorpromoting and co-carcinogenic agent with weak activity as a complete carcinogen. A major effect of promoters, and possibly of co-carcinogens, is a diffuse hyperplasia which includes selective expansion of clones carrying endogenous mutations and/or mutations induced by PAHs and other carcinogens such as NNK. The induced mutations as well as damaged cells would occur throughout the exposed region and, along with the hyperplasia, increase the permissiveness of the cellular microenvironment for neoplastic expression of any potential tumor cell in its midst. Since neither the promoters nor co-carcinogens in tobacco smoke are known to interact directly with DNA, their effects can be considered epigenetic processes that act upon genetically altered cells. Examples are cited from studies of experimental skin carcinogenesis, smoking-induced histopathological changes in human lung and spontaneous transformation in cell culture to illustrate the genetic and epigenetic interactions of neoplastic development in general and their significance for smoking-induced lung cancer in particular. Certain dietary modifications that appear to be effective in moderating the promotional phase of animal and human carcinogenesis are suggested for trial in managing lung cancer.

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“…Usually a sustained chronic exposure to nongenotoxic chemicals at threshold levels and above must be maintained in order for the appearance of a disease state such as cancer to manifest itself (79). Exceptions to this generalization would be the acute exposure to a threshold level of a given nongenotoxic agent or to a mixture of nongenotoxicants at a critical period of embryonic or fetal development (92).…”

mentioning

confidence: 99%

Hierarchical and cybernetic nature of biologic systems and their relevance to homeostatic adaptation to low-level exposures to oxidative stress-inducing agents.

Trosko

1998

Environ Health Perspect

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During evolution in an aerobic environment, multicellular organisms survived by adaptive responses to both the endogenous oxidative metabolism in the cells of the organism and the chemicals and low-level radiation to which they had been exposed. The defense repertoire exists at all levels of the biological hierarchy-from the molecular and biochemical level to the cellular and tissue level to the organ and organ system level. Cells contain preventive antioxidants to suppress oxidative damage to membranes. Cells also contain proteins and DNA; built-in redundancies for damaged molecules and organelles; tightly coupled redox systems; pools of reductants; antioxidants; DNA repair mechanisms and sensitive sensor molecules such as nuclear factor kappa beta; and signal transduction mechanisms affecting both transcription and post-translational modification of proteins needed to cope with oxidative stress. The biologic consequences of the low-level radiation that exceeds the background level of oxidative damage could be necrosis or apoptosis, cell proliferation, or cell differentiation. These effects are triggered by oxidative stress-induced signal transduction mechanisms-an epigenetic, not genotoxic, process. If the end points of cell proliferation, differentiation, or cell death are not seen at frequencies above background levels in an organism, it is unlikely that low-level radiation would play a role in the multistep processes of chronic diseases such as cancer. The mechanism linked to homeostatic regulation of proliferation and adaptive functions in a multicellular organism could provide protection of any one cell receiving deposited energy by the radiation tract through the sharing of reductants and by triggering apoptosis of target stem cells. Examples of the role of gap junctional intercellular communication in the adaptive response of cells and the bystander effect illustrate how the interaction of cells can modulate the effect of radiation on the single cell.

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Correlation between sensitivity to tumor promotion and sustained epidermal hyperplasia of mice and rats treated with 12-O-tetradecanoylphorbol-13-acetate

Cited by 70 publications

References 0 publications

Defective responses of transformed keratinocytes to terminal differentiation stimuli. Their role in epidermal tumour promotion by phorbol esters and by deep skin wounding

Defective responses of transformed keratinocytes to terminal differentiation stimuli. Their role in epidermal tumour promotion by phorbol esters and by deep skin wounding

Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis

Hierarchical and cybernetic nature of biologic systems and their relevance to homeostatic adaptation to low-level exposures to oxidative stress-inducing agents.

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