Topical application of preparations containing DNA repair enzymes prevents ultraviolet-induced telomere shortening and c-FOS proto-oncogene hyperexpression in human skin: an experimental pilot study.

The exposure to ultraviolet radiation (UVR) is one of the most important risk factors for skin aging and increases the risk of malignant transformation. Telomere shortening and an altered expression of the proto-oncogene c-FOS are among the key molecular mechanisms associated with photoaging and tumorigenesis. Photolyase from A. nidulans and endonuclease from M. luteus are xenogenic DNA repair enzymes which can reverse the molecular events associated with skin aging and carcinogenosis caused by UVR exposure. Therefore, the purpose of this study was to investigate whether the topical application of preparations containing DNA repair enzymes may prevent UVR-induced acute telomere shortening and FOS gene hyperexpression in human skin biopsies. Twelve volunteers (Fitzpatrick skin types I and II) were enrolled for this experimental study, and six circular areas (10 mm diameter) were marked out on the nonexposed lower back of each participant. One site was left untreated (site 1: negative control), whereas the remaining five sites (designated sites 2-6) were exposed to solar-simulated UVR at 3 times the MED on four consecutive days. Site 2 received UVR only (site 2: positive control), whereas the following products were applied to sites 3-6, respectively: vehicle (moisturizer base cream; applied both 30 minutes before and immediately after each irradiation; site 3); a traditional sunscreen (SS, SPF 50) 30 minutes before irradiation and a vehicle immediately after irradiation (site 4); a SS 30 minutes before irradiation and an endonuclease preparation immediately after irradiation (site 5); a SS plus photolyase 30 minutes before irradiation and an endonuclease preparation immediately after irradiation (site 6). Skin biopsies were taken 24 h after the last irradiation. The degree of telomere shortening and c-FOS gene expression were measured in all specimens. Strikingly, the combined use of a SS plus photolyase 30 minutes before irradiation and an endonuclease preparation immediately after irradiation completely abrogated telomere shortening and c-FOS gene hyperexpression induced by the experimental irradiations. We conclude that the topical application of preparations containing both photolyase from A. nidulans and endonuclease from M. luteus may be clinically useful to prevent skin aging and carcinogenesis by abrogating UVR-induced telomere shortening and c-FOS gene hyperexpression.

Expression of the immediate early gene, c-fos, in fetal brain after whole of gestation exposure of pregnant mice to global system for mobile communication microwaves.

AIMS: To study immediate early gene, c-fos, expression as a marker of neural stress after whole of gestation exposure of the fetal mouse brain to mobile telephone-type radiofrequency fields. METHODS: Using a purpose-designed exposure system at 900 MHz, pregnant mice were given a single, far-field, whole body exposure at a specific absorption rate of 4 W/kg for 60 min/day from day 1 to day 19 of gestation. Pregnant control mice were sham-exposed or freely mobile in a cage without further restraint. Immediately prior to parturition on gestational day 19, fetal heads were collected, fixed in 4% paraformaldehyde and paraffin embedded. Any stress response in the brain was detected by c-fos immunohistochemistry in the cerebral cortex, basal ganglia, thalamus, hippocampus, midbrain, cerebellum and medulla. RESULTS: c-fos expression was of limited, but consistent, neuroanatomical distribution and there was no difference in immunoreactivity between exposed and control brains. CONCLUSION: In this animal model, no stress response was detected in the fetal brain using c-fos immunohistochemistry after whole of gestation exposure to mobile telephony.

Expression of the immediate early gene, c-fos, in mouse brain after acute global system for mobile communication microwave exposure.

AIMS: To study the effect of acute exposure to global system for mobile communication radiofrequency fields on immediate early gene, c-fos, expression in the brain. METHODS: Using a purpose-designed exposure system at 900 MHz, mice were given a single, far-field, whole body exposure for 60 minutes at a specific absorption rate of 4 W/kg. Control mice were sham-exposed or freely mobile in a cage without further restraint. c-fos protein expression was detected immunohistochemically in perfusion-fixed brains. RESULTS: Activation of c-fos in exposed and sham-exposed brains was comparable, but was greatly increased compared with freely moving controls. CONCLUSION: These results suggest that the majority of the acute genomic response detected by c-fos expression was due to immobilisation rather than irradiation.

Nucleosome positioning in the human c-Fos promoter analyzed by in vivo footprinting with psoralen and ionizing radiation.

We performed detailed footprinting analysis of nucleosome positioning in the c-FOS promoter of living human fibroblasts. The translational position was determined by terminal transferase-dependent PCR with 4,5',8-trimethylpsoralen. The rotational position was determined by ligation-mediated PCR with ionizing radiation. In the middle of the c-FOS promoter, a nucleosome was positioned not only translationally but also rotationally. The comparison of the results of our in vivo footprinting with those of a previous report on the in vitro footprinting of reconstituted nucleosomes revealed that the major in vivo translational position was approximately 70 bp upstream of the in vitro position, whereas the rotational position was unchanged. The in vivo translational position appears to be strongly influenced by the presence of transcription factors, which may function as boundaries, while the rotational position appears to be determined predominantly by the DNA sequence. We also investigated the influence of the transcriptional activation of the c-FOS gene on the positioning of this nucleosome. Although it is well-known that there are rapid changes in general nuclease sensitivity and chemical modifications of histone in the c-FOS gene upon activation, we could not detect any change in the translational or rotational position of this nucleosome. The nucleoprotein complex in the c-FOS promoter containing the positioned nucleosome and several transcription factors seems to be structurally unaltered upon activation, despite the rapid chemical modifications of the nucleosome and some of the transcription factors.

Elliptically polarized magnetic fields do not alter immediate early response genes expression levels in human glioblastoma cells.

Expression of immediate early response genes such as c-fos, c-jun, and c-myc in response to 1-500 microT resultant (r) 60 Hz elliptically polarized (EP) magnetic fields (MFs), typical of environmental MFs polarization under overhead power lines, was analyzed in both at transcriptional and translational levels using human glioblastoma (T98G) cells. Pseudo synchronized T98G cells at G1 phase were exposed to EP-MFs (1, 20, 100, and 500 microTr) for up to 3 h, but produced no statistical difference (P>0.05) in the levels of expression ratio at both the transcriptional and translational levels at 30 min for c-fos and c-jun and at 180 min for c-myc after serum stimulation. In addition, exposure of T98G cells to linearly (vertical and horizontal) and/or circularly polarized MFs (500 microTr) produced no significant change (P>0.05) in the expression ratio at both transcriptional and post-transcriptional levels. Thus, there was no evidence that linearly or rotating polarized MFs enhanced early response gene expression in these studies. These results suggest that environmental MFs at 1-500 microT flux density are unlikely to induce carcinogenesis through a mechanism involving altered expression of the immediate early response genes.

Light-dependent induction of cFos during subjective day and night in PACAP-containing ganglion cells of the retinohypothalamic tract.

Environmental light stimulation via the retinohypothalamic tract (RHT) is necessary for stable entrainment of circadian rhythms generated in the suprachiasmatic nucleus (SCN). In the current report, the authors characterized the functional activity and phenotype of retinal ganglion cells that give rise to the RHT of the rat. Retinal ganglion cells that give rise to the RHT were identified by transsynaptic passage of an attenuated alpha herpesvirus known to have selective affinity for this pathway. Dual labeling immunocytochemistry demonstrated co-localization of viral antigen and pituitary adenylate cyclase activating polypeptide (PACAP) in retinal ganglion cells. This was confirmed using the anterograde tracer cholera toxin subunit B (ChB). In normal and retinally degenerated monosodium glutamate (MSG)-treated rats, ChB co-localized with PACAP in axons of the retinorecipient zone of the SCN. Light-induced Fos-immunoreactivity (Fos-IR) was apparent in all PACAP-containing retinal ganglion cells and a population of non-PACAP-containing retinal ganglion cells at dawn of normal and MSG-treated animals. Within the next 3 h, Fos disappeared in all non-PACAP-immunoreactive cells but persisted in all PACAP-containing retinal ganglion cells until dusk. When animals were exposed to constant light, Fos-IR was sustained only in the PACAP-immunoreactive (PACAP-IR) retinal ganglion cells. Darkness eliminated Fos-IR in all PACAP-IR retinal ganglion cells, demonstrating that the induction of Fos gene expression was light dependent. When animals were maintained in constant darkness and exposed to light pulses at ZT 14, ZT 19, or ZT 6, Fos-IR was induced in PACAP-IR retinal ganglion cells in a pattern similar to that seen at dawn. Collectively, these data indicate that PACAP is present in ganglion cells that give rise to the RHT and suggest a role for this peptide in the light entrainment of the clock.

Role of p38 mitogen-activated protein kinases in ultraviolet-B irradiation-induced activator protein 1 activation in human keratinocytes.

The effects of p38 mitogen-activated protein kinases on ultraviolet (UV) B irradiation-induced activator protein 1 (AP-1) activation were studied in a human keratinocyte cell line, HaCaT. The HaCaT cells were stably transfected with a plasmid containing a promoter fragment of human collagenase 1 driving a luciferase reporter gene. There is an AP-1-binding site within this fragment, without any other known transcription factor-binding sites. As we reported previously, UVB significantly induces activation of AP-1 and p38 in HaCaT cells. SB202190, a p38-specific inhibitor, inhibits UVB-induced p38 activation and c-fos gene expression. In the present study, we further examined the role of p38 in UVB-induced AP-1 activation. We observed that SB202190 strongly inhibited UVB-induced AP-1 transactivation at different time points and UVB doses in transfected HaCaT cells. Furthermore, SB202190 markedly inhibited UVB-induced AP-1 DNA binding as determined by mobility shift analyses. These results suggested, for the first time, that activation of p38 is required for UVB-induced AP-1 activation in human keratinocytes. In addition, a potential mechanism of UVB-induced AP-1 activation through p38 is to enhance AP-1 complex binding to its target DNA. Because c-fos gene expression plays a critical role in UVB-induced AP-1 activation and p38 is required for UVB-induced c-fos gene expression in HaCaT cells, as reported previously, a potential UVB signaling cascade for AP-1 activation in human keratinocytes has been determined. This cascade involves UVB, p38 activation, c-fos gene expression, and AP-1 activation.

UV-Induced stabilization of c-fos and other short-lived mRNAs.

Irradiation of cells with short-wavelength ultraviolet light (UVC) changes the program of gene expression, in part within less than 15 min. As one of the immediate-early genes in response to UV, expression of the oncogene c-fos is upregulated. This immediate induction is regulated at the transcriptional level and is transient in character, due to the autocatalyzed shutoff of transcription and the rapid turnover of c-fos mRNA. In an experiment analyzing the kinetics of c-fos mRNA expression in murine fibroblasts irradiated with UVC, we found that, in addition to the initial transient induction, c-fos mRNA accumulated in a second wave starting at 4 to 5 h after irradiation, reaching a maximum at 8 h, and persisting for several more hours. It was accompanied by an increase in Fos protein synthesis. The second peak of c-fos RNA was caused by an UV dose-dependent increase in mRNA half-life from about 10 to 60 min. With similar kinetics, the mRNAs of other UV target genes (i.e., the Kin17 gene, c-jun, IkappaB, and c-myc) were stabilized (e.g., Kin17 RNA from 80 min to more than 8 h). The delayed response was not due to autocrine cytokine secretion with subsequent autostimulation of the secreting cells or to UV-induced growth factor receptor activation. Cells unable to repair UVC-induced DNA damage responded to lower doses of UVC with an even greater accumulation of c-fos and Kin17 mRNAs than repair-proficient wild-type cells, suggesting that a process in which a repair protein is involved regulates mRNA stability. Although resembling the induction of p53, a DNA damage-dependent increase in p53 was not a necessary intermediate in the stabilization reaction, since cells derived from p53 knockout mice showed the same pattern of c-fos and Kin17 mRNA accumulation as wild-type cells. The data indicate that the signal flow induced by UV radiation addresses not only protein stability (p53) and transcription but also RNA stability, a hitherto-unrecognized level of UV-induced regulation.

Chronic repetitive transcranial magnetic stimulation enhances c-fos in the parietal cortex and hippocampus.

Repetitive transcranial magnetic stimulation (rTMS) is a novel non-invasive method with anti-depressant properties. However, the mechanism of activation on the cellular level is unknown. Twelve hours after the last chronic rTMS treatment (14 days, once per day, 20 Hz, 10 s, 75% machine output, the transcription factor c-fos was markedly increased in neurons in layers I-IV and VI of the parietal cortex and in few scattered neurons in the hippocampus of Sprague-Dawley rats. The cortical activation was not blocked by the NMDA antagonist MK-801. The increase of c-fos was not paralleled by an increased glial response and activation of cortical growth factors. Thus, it is concluded that chronic rTMS differentially activates parietal cortical layers and this might be involved in mediating anti-depressant activity in other brain areas.

Activation of p38 MAP kinase and ERK are required for ultraviolet-B induced c-fos gene expression in human keratinocytes.

The effects of p38 MAP kinase and ERK on UVB induced c-fos gene expression were studied in a human keratinocyte cell line, FL30. UVB significantly increased c-fos gene expression at both the transcriptional and protein levels. p38 and ERK were also significantly activated after UVB irradiation. Treating the cells with p38 inhibitor SB202190 inhibited p38 activation, but not ERK; treating the cells with MEK-1 inhibitor PD98059 inhibited ERK activation without suppressing p38 activation. The kinase activation was determined by Western blots using phospho-p38 or ERK antibodies, or an in vivo p38 activity assay. Further studies demonstrated that blocking p38 almost completely abrogated UVB induced c-fos gene transcription and c-Fos protein synthesis. Inhibiting ERK partially abrogated UVB induced c-fos transcriptional and protein levels. Suppression of both p38 and ERK not only completely blocked UVB induced c-fos expression, but also decreased c-fos gene basal expression. Our data indicated that p38 may play a more important role than ERK in UVB induced c-fos expression in human keratinocytes. Since c-fos expression may play an important role in UVB induced AP-1 activation, and AP-1 activation is known to play a role in tumor promotion, both p38 and ERK could be potential targets for chemoprevention of skin cancer.

Photoprotective effect of black tea extracts against UVB-induced phototoxicity in skin.

In previous studies, we showed that green tea and black tea extracts and their major polyphenolic constituents protect against UVB light-induced carcinogenesis in murine skin. All of these studies required chronic administration of tea extracts or specific constituents either topically or orally. However, it is not known whether acute or subchronic administration of black tea extracts or constituents can ameliorate UVB-induced early effects in skin. In the present study, cultured keratinocytes and mouse and human skin were employed to assess the effect of both oral and topical administration of standardized black tea extract (SBTE) and its two major polyphenolic subfractions namely BTF1 and BTF2 against UVB-induced photodamage. In SKH-1 hairless mice, topical application of SBTE (0.2 mg/cm2) prior to UVB exposure (180 mJ/cm2) resulted in 40% reduced incidence and 64% reduced severity of erythema and 50% reduction in skinfold thickness by day 6 when compared to nontreated UVB-exposed animals. The SBTE was also effective in protecting against UVB-induced erythema in human volunteers. Administration of SBTE 5 min after UVB irradiation was similarly effective in reducing UVB-induced inflammation in both murine and human skin. The major polyphenolic subfractions, BTF1 and BTF2, were also effective in protecting in mouse skin. The SBTE subfractions inhibited UVB-induced tyrosine phosphorylation of epidermal growth factor receptor (EGFR). The UVB irradiation of human epidermoid carcinoma cells resulted in 3.3-fold induction of tyrosine phosphorylation of EGFR. Pretreatment with BTF1 and BTF2 reduced tyrosine phosphorylation of EGFR by 53% and 31%, respectively. The UVB-mediated enhanced expression of the early response genes, c-fos and c-jun in human epidermal keratinocytes was reduced in a dose-dependent manner by SBTE. Topical application of SBTE was also effective in reducing accumulation of c-fos and p53 proteins by 82% and 78%, respectively, in UVB-exposed mouse skin. These data provide evidence that constituents of black tea can abrogate UVB-induced erythema and associated early events in murine and human skin.

IRIDIUM exposure increases c-fos expression in the mouse brain only at levels which likely result in tissue heating.

With the rapid development of wireless communication technology over the last 20 years, there has been some public concern over possible health effects of long-term, low-level radiofrequency exposure from cellular telephones. As an initial step in compiling a database for risk analysis by government agencies, the effects of 1-h exposure of mice to a 1.6-GHz radiofrequency signal, given as either a continuous wave or pulse modulated at 11 Hz with a duty cycle of 4:1 and a pulse duration of 9.2 ms IRIDIUM), on c-fos gene expression in the brain was investigated. The IRIDIUM signal is the operating frequency for a ground-to-satellite-to-ground cellular communications web which has recently become fully operational, and was named as such due to the original designed employment of the same number of low orbiting satellites as there are electrons orbiting the nucleus of an iridium atom. The expression of c-fos was not significantly elevated in the brains of mice until exposure levels exceeded six times the peak dose and 30 times the whole body average dose as maximal cellular telephone exposure limits in humans. Higher level exposure using either continuous wave (analog) or IRIDIUM signals elevated c-fos to a similar extent, suggesting no obvious pulsed modulation-specific effects. The pattern of c-fos elevation in limbic cortex and subcortex areas at higher exposure levels is most consistent with a stress response due to thermal perception coupled with restraint and/or neuron activity near thermoregulatory regions, and not consistent with any direct interaction of IRIDIUM energy with brain tissue.

Activation of expression of the c-fos oncogene by UVA irradiation in cultured human skin fibroblasts.

Both broad-spectrum and near-monochromatic (334 nm, 365 nm and 405 nm) UVA (320-380 nm) and near-visible radiations strongly activate accumulation of mRNA corresponding to the nuclear oncogene and transcription factor, c-fos, in cultured human skin fibroblasts within a dose-range encountered in the environment. The oxidizing component of UVA is clearly of central importance to the activation observed because the absence of reduced glutathione strongly enhances the response. In contrast to observations in rodent cells, we observe negligible activation of the gene in human cells after UVB (290-320 nm) radiation. The results of this study provide evidence that UVA radiation strongly activates c-fos gene expression in human dermal fibroblasts, a phenomena that is likely to be reflected in UVA-mediated modulation of genes containing active AP-1-based enhancer elements in the promoter region.

Inhibition of ultraviolet B--induced c-fos gene expression and p38 mitogen-activated protein kinase activation by (-)-epigallocatechin gallate in a human keratinocyte cell line.

(-)-Epigallocatechin gallate (EGCG), the major polyphenol isolated from green tea, is an active chemoprevention agent against cancer. However, the molecular mechanisms that underlie the inhibitory effects of EGCG are not well understood. In this study, we tested the effects of EGCG on ultraviolet (UV) B radiation-induced c-fos gene expression in a human keratinocyte cell line, HaCaT. EGCG inhibited UVB-induced steady-state message and transcriptional activation of the c-fos gene in a dose-dependent manner. Western analyses further indicated that EGCG had an inhibitory effect on UVB-induced accumulation of the c-fos protein within the same dose range. To further examine the mechanism by which EGCG inhibits UVB-induced c-fos expression, we tested the effect of EGCG on upstream activators of the c-fos gene. We found that EGCG significantly inhibited activation of p38 mitogen-activated protein kinase but not c-jun NH2-terminal kinase or extracellular signal-regulated protein kinase activation. Our previous studies have indicated that UVB-induced c-fos expression may play a key role in UVB-induced activation of the activator protein-1 transcription factor and EGCG-inhibited, UVB-induced activation of AP-1 in HaCaT cells. Because AP-1 is important for tumor promotion and c-fos is a major component of AP-1, the inhibitory effects of EGCG on c-fos expression may further explain the anti-tumor-promoting effects of EGCG.

Proto-oncogene mRNA levels and activities of multiple transcription factors in C3H 10T 1/2 murine embryonic fibroblasts exposed to 835.62 and 847.74 MHz cellular phone communication frequency radiation.

This study was designed to determine whether two differently modulated radiofrequencies of the type generally used in cellular phone communications could elicit a general stress response in a biological system. The two modulations and frequencies studied were a frequency-modulated continuous wave (FMCW) with a carrier frequency of 835.62 MHz and a code division multiple-access (CDMA) modulation centered on 847.74 MHz. Changes in proto-oncogene expression, determined by measuring Fos, Jun, and Myc mRNA levels as well as by the DNA-binding activity of the AP1, AP2 and NF-kappaB transcription factors, were used as indicators of a general stress response. The effect of radiofrequency exposure on proto-oncogene expression was assessed (1) in exponentially growing C3H 10T 1/2 mouse embryo fibroblasts during their transition to plateau phase and (2) during transition of serum-deprived cells to the proliferation cycle after serum stimulation. Exposure of serum-deprived cells to 835.62 MHz FMCW or 847.74 MHz CDMA microwaves (at an average specific absorption rate, SAR, of 0.6 W/kg) did not significantly change the kinetics of proto-oncogene expression after serum stimulation. Similarly, these exposures did not affect either the Jun and Myc mRNA levels or the DNA-binding activity of AP1, AP2 and NF-kappaB in exponential cells during transit to plateau-phase growth. Therefore, these results suggest that the radiofrequency exposure is unlikely to elicit a general stress response in cells of this cell line under these conditions. However, statistically significant increases (approximately 2-fold, P = 0.001) in Fos mRNA levels were detected in exponential cells in transit to the plateau phase and in plateau-phase cells exposed to 835.62 MHz FMCW microwaves. For 847.74 MHz CDMA exposure, the increase was 1.4-fold (P = 0.04). This increase in Fos expression suggests that expression of specific genes could be affected by radiofrequency exposure.

Environmental light enhances survival and axonal regeneration of axotomized retinal ganglion cells in adult cats.

A segment of peripheral nerve was transplanted to the cut stump of the optic nerve to facilitate axonal regeneration of retinal ganglion cells (RGCs) in adult cats. The cats were reared under different light environment: 12 h light-12 h darkness, additional flash light under conventional light cycle, or 24 h darkness. After 60 days, the density and morphology of RGCs with regenerated axons were examined with retrograde labeling by fluoro-ruby and intracellular injections of Lucifer Yellow. In the retina of cats reared in darkness, densities of RGCs with regenerated axons were 11-42% of those in the retina of cats reared under conventional light and dark cycle. More than half of the labeled RGCs were degenerative in the retina of cats reared in darkness, while most RGCs were normal under conventional environment or flash light. We conclude that environmental light is essential for the survival and axonal regeneration of axotomized RGCs.

Repetitive transcranial magnetic stimulation activates specific regions in rat brain.

Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

UVB irradiation-induced activator protein-1 activation correlates with increased c-fos gene expression in a human keratinocyte cell line.

The effects of UVB irradiation on transcription factor activator protein-1 (AP-1) DNA binding and AP-1 transactivation were studied in a human keratinocyte cell line, HaCaT. UVB-induced AP-1 binding to a consensus AP-1 binding site was observed by gel shift assays with maximum stimulation at 12 h after UVB irradiation. A promoter region of the human collagenase-1 gene containing the same AP-1 binding sequence linked to a luciferase reporter gene was stably transfected into HaCaT cells. UVB irradiation significantly increased luciferase activity in these stably transfected cells, with maximum activity observed at 24 h after UVB irradiation. c-Fos and Jun D were identified by antibody clearing assays as the main components of the bound AP-1 complexes. Inhibition of transcription with actinomycin D and inhibition of protein synthesis with cycloheximide significantly abrogated the effect of UVB on AP-1 DNA binding, indicating that transcription and translation were required for AP-1 activation. Northern and Western analyses revealed a correlation between increased AP-1 activity and accumulation of c-fos mRNA and c-Fos protein after UVB irradiation. UVB irradiation increased c-fos transcription in HaCaT cells stably transfected with a plasmid containing the human c-fos promoter driving a luciferase reporter gene. These results suggest that increased c-fos expression may play an important role in UVB-induced AP-1 activation in HaCaT cells.

Light affects c-fos expression and phospholipid synthesis in both retinal ganglion cells and photoreceptor cells in an opposite way for each cell type.

Retina photoreceptor and ganglion cells isolated from chicks that in vivo were exposed to light have a different phospholipid labeling capacity than those from chicks in the dark. In the light exposed animals, the phospholipid labeling in the ganglion cells is higher (Delta% 45, p<0.005) than in those maintained in the dark, whereas in the photoreceptor cells, the opposite occurs, that is, the phospholipid labeling is higher in the dark than in light. The light-dark differences for phospholipid labeling correlate with the expression of c-fos: when c-fos expression increases (both in mRNA and in c-Fos protein content), phospholipid labeling increases concomitantly. That is, in ganglion cells, c-fos expression and the phospholipid synthesis is higher in light with respect to dark, whereas in photoreceptor cells, c-fos expression and phospholipid synthesis is higher in dark with respect to light. Moreover, when an oligonucleotide antisense to c-fos is administered intraocularly prior to separating the animals into light and dark, no differences in c-fos expression and, consequently, no differences in phospholipid synthesis are found between animals in light and dark. Taken together, these results point to a novel mechanism by which rapid genomic responses to cell stimulation are converted to longer lasting changes in the cell components.