High dietary retinoic acid inhibits tumor promotion and malignant conversion in a two-stage skin carcinogenesis protocol using 7,12-dimethylbenz[a]anthracene as the initiator and mezerein as the tumor promoter in female SENCAR mice

Chen, Li Chuan; Tarone, Robert E.; Huynh, Minh Q.; Luca, Luigi M. De

doi:10.1016/0304-3835(95)03868-w

Cited by 12 publications

(6 citation statements)

References 7 publications

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“…Dietary retinoid intake has been associated with a reduction in the incidence of a number of cancers, although recent clinical trials have raised some questions as to the validity of this relationship in at least some cases (Altucci and Gronemeyer, 2001;Sun and Lotan, 2002). In animal models, RA can inhibit papilloma formation and malignant conversion in chemical carcinogenesis protocols (Chen et al, 1995;De Luca et al, 1996). These observations imply that RARs may play key roles in skin carcinogenesis.…”

Section: Discussionmentioning

confidence: 91%

RARγ acts as a tumor suppressor in mouse keratinocytes

2004

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All-trans retinoic acid (RA), the principal biologically active form of vitamin A, is essential for many developmental process as well as homeostasis in the adult. Many lines of evidence also suggest that RA, acting through the RA receptors (RARs), can also suppress growth of tumors of diverse origin. To assess directly the role of the RARs in a model of epidermal tumorigenesis, we investigated the incidence of tumor formation using keratinocytes lacking specific RAR types. Our data suggest that loss of RARc, but not RARa, predisposed keratinocytes to v-Ha-Rasinduced squamous cell carcinoma. We also found that ablation of RARc, but not RARa, abolished RA-induced cell cycle arrest and apoptosis in these keratinocytes. Reconstitution of receptor expression into RAR-null cells restored sensitivity to RA, and reversed the tumorigenic potential of receptor-deficient keratinocytes. These data strongly support a tumor suppressor effect for the RARs, in particular endogenous RARc, in murine keratinocytes.

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Section: Discussionmentioning

confidence: 91%

RARγ acts as a tumor suppressor in mouse keratinocytes

2004

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“…The SENCAR mouse with topical chemical carcinogen treatment is a commonly used model of skin cancer (Chen et al, 1995;Galvez et al, 2001). It is worth pointing out that the 2 H 2 O labeling method was able to detect a dramatic increase in epidermal cell proliferation rate within 3 wk of carcinogen treatment.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of Keratinocytes in Vivo using 2H2O Labeling: A Sensitive Marker of Epidermal Proliferation State

Hsieh

Chai

Lumen

et al. 2004

Journal of Investigative Dermatology

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A heavy water ((2)H(2)O) labeling method recently developed to measure cell proliferation in vivo is applied here to the measurement of murine epidermal cell turnover and to investigate conditions in which keratinocyte proliferation is either inhibited or stimulated. The technique is based on incorporation of (2)H(2)O into the deoxyribose moiety of deoxyribonucleotides in dividing cells. Label incorporation and die-away studies in cells isolated from C57BL/6J mouse epidermis revealed the replacement rate to be 34%-44% per wk (half-life of 1.6-2 wk). The kinetics provided evidence of a non-proliferative subpopulation of cells (10%-15% of the total) within the epidermis. Topical administration of 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol-13-acetate for 3 wk increased epidermal cell proliferation by 55% in SENCAR mice. Topical addition of lunasin, an anti-mitotic agent from soy, decreased epidermal cell proliferation modestly though significantly (16% given alone, 9% given with carcinogens). Caloric restriction (by 33% of energy intake) for 4 wk decreased the epidermal cell proliferation rate by 45% in C57BL/6J mice. In summary, epidermal cell proliferation can be measured in vivo using (2)H(2)O labeling in normal, hyper- and hypo-proliferative conditions. Potential applications of this inherently safe method in humans might include studies of psoriasis, wound healing, chemopreventive agents, and caloric intake.

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“…Further, SENCAR mice fed a vitamin A–deficient diet developed splenomegaly earlier than both NIH and the Balb/c mice fed an equally deficient diet ( 43 ). Interestingly, the SENCAR mouse has also been used to study the chemopreventive activity of retinoids, both applied topically and given in the diet ( 42 , 44 , 45 ).…”

Section: Discussionmentioning

confidence: 99%

Immunodeficiency Accelerates Vitamin A Deficiency

Luca¹,

Petrides²,

Darwiche³

et al. 2021

Current Developments in Nutrition

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Background Vitamin A deficiency increases susceptibility to infection caused by impaired immune function. Objectives We investigated whether immunodeficiency could facilitate the development of vitamin A deficiency. Methods Vitamin A deficiency was followed in 2 mouse models of immunodeficiency: the athymic nude mouse (nu/nu) and the humoral immunodeficient SENCAR (SENsitive to CARcinogenesis) mouse. Vitamin A deficiency was also monitored in outbred Balb/c and in NIH mice. The monitoring of vitamin A deficiency was done after feeding the mice and their mothers a semisynthetic, vitamin A–deficient diet from birth of the experimental mice. These mice were weaned onto the same deficient diet at 3–4 wk of age, while control groups were fed the same diet containing 3 μg retinoic acid per gram of diet. Results The immunodeficient nu/nu and SENCAR mice developed vitamin A deficiency earlier than either the heterozygous nu/+ controls or the Balb/c and NIH strains. In female mice, symptoms included depletion of liver retinol and retinyl palmitate, squamous metaplasia of the uterus, and death. Male mice lost weight more frequently and sooner than female mice, in which mortality generally occurred in the absence of loss of body weight. Pairwise comparisons using Tukey's honest significant difference test of the nu/nu and SENCAR mice versus the Balb/c and NIH mice showed a faster loss of retinol and retinyl palmitate in all pairs (P ≤ 0.0001) except for retinol when comparing nu/nu and NIH strains (P = 0.3383). Conclusions Our findings are consistent with an increased usage of liver retinol and retinyl palmitate in the immunocompromised nu/nu and in the immunodeficient SENCAR mice and suggest that compensatory mechanisms dependent on vitamin A utilization are called upon to rescue immunodeficiency both in the T-cell–deficient phenotype of the nu/nu mice and in the humoral immunodeficient SENCAR mice.

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High dietary retinoic acid inhibits tumor promotion and malignant conversion in a two-stage skin carcinogenesis protocol using 7,12-dimethylbenz[a]anthracene as the initiator and mezerein as the tumor promoter in female SENCAR mice

Cited by 12 publications

References 7 publications

RARγ acts as a tumor suppressor in mouse keratinocytes

RARγ acts as a tumor suppressor in mouse keratinocytes

Dynamics of Keratinocytes in Vivo using 2H2O Labeling: A Sensitive Marker of Epidermal Proliferation State

Immunodeficiency Accelerates Vitamin A Deficiency

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