Apoptosis and cancer risk assessment

Goldsworthy, Thomas L.; Conolly, Rory B.; Fransson-Steen, Ronny

doi:10.1016/s0165-1110(96)90013-5

Cited by 70 publications

(33 citation statements)

References 73 publications

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“…A growth imbalance in favor of cell proliferation has been proposed to be related to benign prostatic hyperplasia, 15 and in the development of malignant tumors. 16 Thus, the comparison of the cell kinetics of these tissues may aid in understanding the different proliferative pattern of these organs. In our study, the proliferative index of the normal prostatic tissue was 0.77 and the apoptotic index was 0.73, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…25 On the other hand, it is suspected that apoptosis will eliminate mutated or damaged cells from the organism and will therefore play a role in cancer prevention. 16 In this case, not just the proliferation rate, but the relation between the proliferative index and the apoptotic index will play an important role in carcinogenesis. 24 On the other hand, some studies demonstrated that the apoptosis rate was elevated in preneoplastic cells compared to normal cells from the same tissue.…”

Section: Discussionmentioning

confidence: 99%

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Cell turnover in human seminal vesicles and the prostate: an immunohistochemical study

Pannek

Berges

Sauvageot³

et al. 1999

Prostate Cancer Prostatic Dis

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The human prostate and seminal vesicles are both androgen-dependent sex accessory organs. Their growth behavior, response to hormone manipulation, susceptibility to benign and malignant processes and sex accessory functions, however, differ greatly. The growth behavior of most tissues correlates well with the cell turnover rate of that tissue. Therefore, we compared the cell turnover of normal human prostate and seminal vesicles.Immunohistochemical expression of MIB-1 (proliferation), bcl-2 and transforming growth factor (TGF b) were examined in 20 different samples taken from histologically normal human prostatic and seminal vesicle tissue. For the quanti®cation of apoptosis, the TUNEL technique was used.The apoptosis rates in normal prostatic tissue (0.73 AE 0.60) were signi®cantly greater (P 0.003) than those seen in seminal vesicles (0.02 AE 0.01). The proliferation rates also differed signi®cantly (P 0.002) between these tissues (prostate: 0.77 AE 0.78; seminal vesicles: 0.02 AE 0.02). Eighty percent of the prostate tissue stained for bcl-2, whereas only 55% of the seminal vesicle tissue showed staining for bcl-2. All seminal vesicles and 75% of the prostate samples stained for TGF b b. For both androgen-dependent tissues, apoptotic rates closely equaled proliferation rates. The cell turnover, however, was much higher in the prostate than in the seminal vesicles. TGF b seems to be more important for the regulation of cell turnover in the seminal vesicles than bcl-2. These differences in the proliferative behavior may explain why disturbances of apoptotic regulation lead to a more extensive net cell gain in prostatic tissue compared to the seminal vesicles. This might help explain the vastly different incidence of benign and malignant tumors in these organs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cell turnover in human seminal vesicles and the prostate: an immunohistochemical study

Pannek

Berges

Sauvageot³

et al. 1999

Prostate Cancer Prostatic Dis

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“…Thus, there is simultaneous cell loss and replacement revealed on three levels: on the cellular level by apoptosis and mitosis, on the histologic level by tubular atrophy and hyperplasia (regeneration), and grossly by decreased kidney weight (Figure 4). The failure of regeneration to keep pace with cell loss may be quite important, as imbalances between cell loss and replacement in tissues may be a significant contributor to carcinogenesis (76)(77)(78).…”

Section: Nephrotoxicitymentioning

confidence: 99%

An overview of rodent toxicities: liver and kidney effects of fumonisins and Fusarium moniliforme.

Voss

Riley

Norred

et al. 2001

Environ Health Perspect

121

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Fumonisins are produced by Fusarium moniliforme F. verticillioides) and other Fusarium that grow on corn worldwide. They cause fatal toxicoses of horses and swine. Their effects in humans are unclear, but epidemiologic evidence suggests that consumption of fumonisin-contaminated corn contributes to human esophageal cancer in southern Africa and China. Much has been learned from rodent studies about fumonisin B1(FB1), the most common homologue. FB1 is poorly absorbed and rapidly eliminated in feces. Minor amounts are retained in liver and kidneys. Unlike other mycotoxins, fumonisins cause the same liver cancer promotion and subchronic (studies (3/4) 90 days) liver and kidney effects as (italic)F. moniliforme. FB 1 induces apoptosis of hepatocytes and of proximal tubule epithelial cells. More advanced lesions in both organs are characterized by simultaneous cell loss (apoptosis and necrosis) and proliferation (mitosis). Microscopic and other findings suggest that an imbalance between cell loss and replacement develops, a condition favorable for carcinogenesis. On the molecular level, fumonisins inhibit ceramide synthase, and disrupt sphingolipid metabolism and, theoretically, sphingolipid-mediated regulatory processes that influence apoptosis and mitosis. Liver sphingolipid effects and toxicity are correlated, and ceramide synthase inhibition occurs in liver and kidney at doses below their respective no-observed-effect levels. FB1 does not cross the placenta and is not teratogenic in vivoin rats, mice, or rabbits, but is embryotoxic at high, maternally toxic doses. These data have contributed to preliminary risk evaluation and to protocol development for carcinogenicity and chronic toxicity studies of FB1 in rats and mice.

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“…Tissue hypertrophy or atrophy is the direct result of chronic imbalance in rates of cell proliferation and death (2) (18). The importance of proliferation as a major risk factor may only become significant when it is liberated from the constraints imposed by apoptosis, i.e., when it becomes truly uncontrolled.…”

Section: Homeostatic Balance Between Apoptosis and Proliferation Lowementioning

confidence: 99%

“…In a recent series of studies, we tested the hypothesis that a relative increase in the basal rate of apoptosis with DR may contribute to the mechanisms of tumor resistance and prolongation of life span by promoting natural selection at the cellular level. Spontaneous rates of apoptosis and proliferation were quantified in liver sections from 12-month-old DR and AL-fed male B6C3F1 mice, a murine strain with increased genetic susceptibility to developing spontaneous liver tumors by 18 months of age (36). The DR group received 60% of the AL consumption of an NIH-31 open-formula diet supplemented with vitamins to ensure equal micronutrient consumption between groups.…”

Section: Homeostatic Balance Between Apoptosis and Proliferation Lowementioning

confidence: 99%

Upregulation of Apoptosis with Dietary Restriction: Implications for Carcinogenesis and Aging

James¹,

Muskhelishvili²,

Gaylor³

et al. 1998

Environmental Health Perspectives

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The maintenance of cell number homeostasis in normal tissues reflects a highly regulated balance between the rates of cell proliferation and cell death. Under pathologic conditions such as exposure to cytotoxic, genotoxic, or nongenotoxic agents, an imbalance in these rates may indicate subsequent risk of carcinogenesis. Apoptotic cell death, as opposed to necrotic cell death, provides a protective mechanism by selective elimination of senescent, preneoplastic, or superfluous cells that could negatively affect normal function and/or promote cell transformation. The relative efficiency or dysfunction of the cell death program could therefore have a direct impact on the risk of degenerative or neoplastic disease. Dietary restriction of rodents is a noninvasive intervention that has been reproducibly shown to retard tumor development and most physiologic indices of aging relative to ad libitum-fed animals. As such, it provides a powerful model in which to study common mechanistic processes associated with both aging and cancer. In a recent study we established that chronic dietary restriction (DR) induces an increase in spontaneous apoptotic rate and a decrease in cell proliferation rate in hepatocytes of 1 2-month-old B6C3F1 DR mice relative to ad libitum (AL)-fed mice. This diet-induced shift in cell death/proliferation rates was associated with a marked reduction in subsequent development of spontaneous hepatoma and a marked increase in disease-free life span in DR relative to AL-fed mice. These results suggest that total caloric intake may modulate the rates of cell death and proliferation in a direction consistent with a cancer-protective effect in DR mice and a cancerpromoting effect in AL mice. To determine whether the increase in spontaneous apoptotic rate was maintained over the life span of DR mice, apoptotic rates were quantified in 12-, 18-, 24-and 30-month-old DR and AL mice. The rate of apoptosis was elevated with age in both diet groups; however, the rate of apoptosis was significantly and consistently higher in DR mice regardless of age. In double-labeling experiments, an age-associated increase in the glutathione S-transferase-ll expression in putative preneoplastic hepatocytes in AL mice was rapidly reduced by apoptosis upon initiation of DR. Thus, interventions that promote a low-level increase in apoptotic cell death may be expected to protect genotypic and phenotypic stability with age. If during tumor promotion an adaptive increase in apoptosis effectively balances the dysregulated increase proliferation, the risk of permanent genetic error and carcinogenesis would be minimized.Environ Health Perspect 106(Suppl 1): 307-312 (1998). http://ehpnetl.niehs.nih.gov/docs/1998/Suppl-1/ 307-312james/abstract.html

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Apoptosis and cancer risk assessment

Cited by 70 publications

References 73 publications

Cell turnover in human seminal vesicles and the prostate: an immunohistochemical study

Cell turnover in human seminal vesicles and the prostate: an immunohistochemical study

An overview of rodent toxicities: liver and kidney effects of fumonisins and Fusarium moniliforme.

Upregulation of Apoptosis with Dietary Restriction: Implications for Carcinogenesis and Aging

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