Caffeine Research Today is a free monthly online journal that collates and summarizes the latest research about Caffeine, including details on addiction, drugs, effects, coffee.

Effect of caffeine on the ATR/Chk1 pathway in the epidermis of UVB-irradiated mice.

Lu YP, Lou YR, Peng QY, Xie JG, Nghiem P, Conney AH

Susan Lehman Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854-8020, USA.

Administration of caffeine was shown in earlier studies to enhance UVB-induced apoptosis and inhibit UVB-induced carcinogenesis in hairless SKH-1 mice. Here, we describe a potential mechanism for these in vivo effects. A single irradiation of mouse skin with UVB activated the ataxia-telangiectasia mutated- and Rad3-related (ATR) pathway, causing a severalfold increase in keratinocytes with phospho-Chk1 (Ser(345)) and a marked decrease in mitotic keratinocytes with cyclin B1 compared with baseline. When given in the drinking water for 1 to 2 weeks before UVB, caffeine (0.4 mg/mL) markedly inhibited the UVB-induced phosphorylation of Chk1 on Ser(345) and caused premature expression of cyclin B1 in the epidermis. Normal keratinocytes had delayed mitotic entry for >10 h following UVB. Caffeine administration reduced this mitotic delay to only 4 h and caused markedly increased apoptosis by 6 to 10 h after UVB. p53 knockout mice were used to determine the role of p53 in these processes. Irradiation with UVB markedly decreased the number of mitotic keratinocytes with cyclin B1 in p53 knockout mice, and topical caffeine immediately after UVB abrogated this response and increased UVB-induced apoptosis severalfold. These effects of caffeine in knockout mice were substantially greater than in wild-type mice. The ability of caffeine to promote the deletion of p53(-/-) keratinocytes may be relevant to its inhibitory effect on UVB-induced skin cancer. Our studies indicate that administration of caffeine enhances the removal of DNA-damaged cells by inhibiting the ATR-mediated phosphorylation of Chk1 and prematurely increasing the number of cyclin B1-containing cells that undergo lethal mitosis.

Published 2 April 2008 in Cancer Res, 68(7): 2523-9.
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Articles on Caffeine published 2 April 2008:

Protective versus promotional effects of white tea and caffeine on PhIP-induced tumorigenesis and beta-catenin expression in the rat.   Carcinogenesis, 29(4): 834-9.

A 1 year carcinogenicity bioassay was conducted in rats treated with three short cycles of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)/high-fat (HF) diet, followed by 2% white tea (wt/vol), 0.05% epigallocatechin-3-gallate (EGCG) or 0.065% caffeine as sole source of fluid intake. Thirty-two percent of the PhIP/HF controls survived to 1 year, compared with 50, 48.7 and 18.2% in groups given white tea, EGCG and caffeine, respectively. After 1 year, PhIP/HF controls had tumors in the ... [Abstract] [Full-text]

Articles on Caffeine published 17 March 2008:

Relative contribution of rat cytochrome P450 isoforms to the metabolism of caffeine: the pathway and concentration dependence.   Biochem Pharmacol, 75(7): 1538-49.

The aim of the present study was to estimate the relative contribution of rat P450 isoforms to the metabolism of caffeine and to assess the usefulness of caffeine as a marker substance for estimating the activity of P450 in rat liver and its potential for pharmacokinetic interactions in pharmacological experiments. The results obtained using rat cDNA-expressed P450s indicated that 8-hydroxylation was the main oxidation pathway of caffeine (70%) in the rat. CYP1A2 was found to be a key enzyme ... [Abstract] [Full-text]

Articles on Caffeine published 14 March 2008:

Habitual caffeine intake in women of childbearing age.   J Hum Nutr Diet, 21(2): 159-64.

BACKGROUND: For women, delayed conception and recurrent pregnant loss are just a few of the health implications associated with a caffeine-rich diet (Mol. Hum. Reprod., 11, 357). At present there is a deficit of prospective research measuring current habitual intakes of caffeine in UK women. The purpose of the current study was to collect up-to-date baseline data to assess caffeine intake and knowledge in a group of women (aged 16-45 years). METHODS: Seventy Caucasian subjects (mean age 30.4 ... [Abstract] [Full-text]

Articles on Caffeine published 3 March 2008:

Maternal caffeine consumption during pregnancy and the risk of miscarriage: a prospective cohort study.   Am J Obstet Gynecol, 198(3): 279.e1-8.

OBJECTIVE: The objective of the study was to examine whether the risk of miscarriage is associated with caffeine consumption during pregnancy after controlling for pregnancy-related symptoms. STUDY DESIGN: This was a population-based prospective cohort study. RESULTS: An increasing dose of daily caffeine intake during pregnancy was associated with an increased risk of miscarriage, compared with no caffeine intake, with an adjusted hazard ratio (aHR) of 1.42 (95% confidence interval 0.93 to ... [Abstract] [Full-text]

Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer.   Cancer, 112(5): 1169-77.

BACKGROUND: Smoking, caffeine, and alcohol intake are all potentially modifiable factors that have an unclear association with ovarian cancer risk. Therefore, the associations between these exposures and ovarian cancer risk were prospectively examined among 110,454 women in the Nurses' Health Study (NHS) for the smoking analyses and 80,253 women for the dietary analyses. METHODS: Women completed biennial questionnaires assessing ovarian cancer risk factors beginning in 1976, with food frequency ... [Abstract] [Full-text]

Coffee, tea, caffeine and risk of breast cancer: a 22-year follow-up.   Int J Cancer, 122(9): 2071-6.

The relation between consumption of coffee, tea and caffeine and risk of breast cancer remains unsettled. We examined data from a large, long-term cohort study to evaluate whether high intake of coffee and caffeine is associated with increased risk of breast cancer. This was a prospective cohort study with 85,987 female participants in the Nurses' Health Study. Consumption of coffee, tea and caffeine consumption was assessed in 1980, 1984, 1986, 1990, 1994, 1998 and the follow-up continued ... [Abstract] [Full-text]

Articles on Caffeine published 29 February 2008:

Effect of single loading dose of intravenous caffeine infusion on superior mesenteric artery blood flow velocities in preterm infants.   J Paediatr Child Health, 44(3): 119-21.

AIM: To evaluate the effects of a single loading dose of caffeine base (10 mg/kg) on superior mesenteric artery (SMA) blood flow velocities (BFV). METHODS: Eighteen preterm infants of gestational age <or=32 weeks gestation were investigated prospectively. SMA BFV before infusion, 1 h, 2 h and 6 h after a single loading dose of caffeine were measured using Doppler ultrasonography. RESULTS: The peak systolic velocity in SMA decreased by 18% from baseline at 1 h after caffeine infusion and ... [Abstract] [Full-text]

Caffeine-induced hyperactivity in the horse: comparisons of drug and metabolite concentrations in blood and cerebrospinal fluid.   J Vet Pharmacol Ther, 31(2): 156-66.

The goals of this study were to elucidate the temporal and quantitative relationships between caffeine and its major bioactive metabolites in blood and cerebrospinal fluid (CSF) and to characterize the pharmacokinetic-pharmacodynamic relationship for caffeine-induced changes in spontaneous locomotor activity in the horse. We hypothesized that caffeine and its metabolites distribute efficiently into the CSF to antagonize adenosine A1 and A2a receptors and that spontaneous locomotor activity ... [Abstract] [Full-text]

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