Mouse Harderian Gland Research Articles

Harderian Gland Development and Degeneration in the Fgf10-Deficient Heterozygous Mouse.

The mouse Harderian gland (HG) is a secretory gland that covers the posterior portion of the eyeball, opening at the base of the nictitating membrane. The HG serves to protect the eye surface from infection with its secretions. Mice open their eyelids at about 2 weeks of age, and the development of the HG primordium mechanically opens the eye by pushing the eyeball from its rear. Therefore, when HG formation is disturbed, the eye exhibits enophthalmos (the slit-eye phenotype), and a line of Fgf10+/- heterozygous loss-of-function mice exhibits slit-eye due to the HG atrophy. However, it has not been clarified how and when HGs degenerate and atrophy in Fgf10+/- mice. In this study, we observed the HGs in embryonic (E13.5 to E19), postnatal (P0.5 to P18) and 74-week-old Fgf10+/- mice. We found that more than half of the Fgf10+/- mice had markedly degenerated HGs, often unilaterally. The degenerated HG tissue had a melanized appearance and was replaced by connective tissue, which was observed by P10. The development of HGs was delayed or disrupted in the similar proportion of Fgf10+/- embryos, as revealed via histology and the loss of HG-marker expression. In situ hybridization showed Fgf10 expression was observed in the Harderian mesenchyme in wild-type as well as in the HG-lacking heterozygote at E19. These results show that the Fgf10 haploinsufficiency causes delayed or defective HG development, often unilaterally from the unexpectedly early neonatal period.

Stimulated Microgravity Affects Mitochondrial Homeostasis in the Harderian Glands of Mice

Stimulated Microgravity Affects Mitochondrial Homeostasis in the Harderian Glands of Mice

Capsazepine decreases corneal pain syndrome in severe dry eye disease

BackgroundDry eye disease (DED) is a multifactorial disease of the ocular surface accompanied by neurosensory abnormalities. Here, we evaluated the effectiveness of transient receptor potential vanilloid-1 (TRPV1) blockade to alleviate ocular pain, neuroinflammation, and anxiety-like behavior associated with severe DED.MethodsChronic DED was induced by unilateral excision of the Harderian and extraorbital lacrimal glands of adult male mice. Investigations were conducted at 21 days after surgery. The mRNA levels of TRPV1, transient receptor potential ankyrin-1 (TRPA1), and acid-sensing ion channels 1 and 3 (ASIC1 and ASIC3) in the trigeminal ganglion (TG) were evaluated by RNAscope in situ hybridization. Multi-unit extracellular recording of ciliary nerve fiber activity was used to monitor spontaneous and stimulated (cold, heat, and acid) corneal nerve responsiveness in ex vivo eye preparations. DED mice received topical instillations of the TRPV1 antagonist (capsazepine) twice a day for 2 weeks from d7 to d21 after surgery. The expression of genes involved in neuropathic and inflammatory pain was evaluated in the TG using a global genomic approach. Chemical and mechanical corneal nociception and spontaneous ocular pain were monitored. Finally, anxiety-like behaviors were assessed by elevated plus maze and black and white box tests.ResultsFirst, in situ hybridization showed DED to trigger upregulation of TRPV1, TRPA1, ASIC1, and ASIC3 mRNA in the ophthalmic branch of the TG. DED also induced overexpression of genes involved in neuropathic and inflammatory pain in the TG. Repeated instillations of capsazepine reduced corneal polymodal responsiveness to heat, cold, and acidic stimulation in ex vivo eye preparations. Consistent with these findings, chronic capsazepine instillation inhibited the upregulation of genes involved in neuropathic and inflammatory pain in the TG of DED animals and reduced the sensation of ocular pain, as well as anxiety-like behaviors associated with severe DED.ConclusionThese data provide novel insights on the effectiveness of TRPV1 antagonist instillation in alleviating abnormal corneal neurosensory symptoms induced by severe DED, opening an avenue for the repositioning of this molecule as a potential analgesic treatment for patients suffering from chronic DED.

Modeling Radiation-Induced Neoplastic Cell Transformation In Vitro and Tumor Induction In Vivo with the Local Effect Model.

Ionizing radiation induces DNA damage to cycling cells which, if left unrepaired or misrepaired, can cause cell inactivation or heritable, viable mutations. The latter can lead to cell transformation, which is thought to be an initial step of cancer formation. Consequently, the study of radiation-induced cell transformation promises to offer insights into the general properties of radiation carcinogenesis. As for other end points, the effectiveness in inducing cell transformation is elevated for radiation qualities with high linear energy transfer (LET), and the same is true for cancer induction. In considering DNA damage as a common cause of both cell death and transformations, a worthwhile approach is to apply mathematical models for the relative biological effectiveness (RBE) of cell killing to also assess the carcinogenic potential of high-LET radiation. In this work we used an established RBE model for cell survival and clinical end points, the local effect model (LEM), to estimate the transformation probability and the carcinogenic potential of ion radiation. The provided method consists of accounting for the competing processes of cell inactivation and induction of transformations or carcinogenic events after radiation exposure by a dual use of the LEM. Correlations between both processes inferred by the number of particle impacts to individual cells were considered by summing over the distribution of hits that individual cells receive. RBE values for cell transformation in vitro were simulated for three independent data sets, which were also used to gauge the approach. The simulations reflect the general RBE systematics both in magnitude and in energy and LET dependence. To challenge the developed method, in vivo carcinogenesis was investigated using the same concepts, where the probability for cancer induction within an irradiated organ was derived from the probability of finding carcinogenic events in individual cells. The predictions were compared with experimental data of carcinogenesis in Harderian glands of mice. Again, the developed method shows the same characteristics as the experimental data. We conclude that the presented method is helpful to predictively assess RBE for both neoplastic cell transformation and tumor induction after ion exposure within a wide range of LET values. The theoretical concept requires a non-linear component in the photon dose response for carcinogenic end points as a precondition for the observed enhanced effects after ion exposure, thus contributing to a long debate in epidemiology. Future work will use the method for assessing cancer induction in radiation therapy and exposure scenarios frequently discussed in radiation protection.

Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-set for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.

Animal Studies of Charged Particle-induced Carcinogenesis

The distribution of energy deposition in cells and tissues by high-charge, high-energy (HZE) nuclei differs considerably from that of low linear energy transfer (LET) radiation, raising concerns that charged particle exposure may be more efficient in inducing radiogenic cancers or may induce a different spectrum of tumors. The authors have performed a review of charged particle carcinogenesis in animals with the following observations. A limited number of animal studies with carcinogenesis endpoints have been performed to evaluate the effectiveness of HZE ions. These include the induction of skin and mammary tumors in the rat and Harderian gland tumors, acute myeloid leukemia (AML), and hepatocellular carcinomas in the mouse. In general, high relative biological effectiveness (RBE) has been reported for solid tumor induction. RBE dependence on HZE radiation quality has been most extensively characterized in studies of mouse Harderian gland tumorigenesis. In this model, the RBE increases with LET and plateaus in the 193-953 keV μm(-1) range. Unlike the results of solid tumor studies, a leukemogenesis study found 1 GeV nucleon(-1) 56Fe ions no more efficient than gamma-rays for AML induction. No novel tumor types have been observed in HZE irradiated animals as compared with those that occur spontaneously or following low-LET radiation exposures. Genetic background of the irradiated animals is critical; the tumor types induced in HZE irradiated mice depend on their strain background, and the incidence of HZE ion-induced mammary carcinogenesis in the rat is also strain dependent.

Carbonic anhydrases in the mouse harderian gland

The harderian gland is located within the orbit of the eye of most terrestrial vertebrates. It is especially noticeable in rodents, in which it synthesises lipids, porphyrins, and indoles. Various functions have been ascribed to the harderian gland, such as lubrication of the eyes, a site of immune response, and a source of growth factors. Carbonic anhydrases (CAs) are zinc-containing metalloenzymes that catalyse the reaction CO₂ + H₂O <--> H+ + HCO₃. They are involved in the adjustment of pH in the secretions of different glands. Thirteen enzymatically active isozymes have been described in the mammalian α-CA family. Here, we first investigated the mRNA expression of all 13 active CAs in the mouse harderian gland by quantitative real-time PCR. Nine CA mRNAs were detectable in the gland. Car5b and Car13 showed the highest signals. Car4, Car6, and Car12 showed moderate expression levels, whereas Car2, Car3, Car7, and Car15 mRNAs were barely within the detection limits. Immunohistochemical staining was performed to study the expression of Car2, Car4, Car5b, Car12, and Car13 at the protein level. The epithelial cells were intensively stained for CAVB, whereas only weak signal was detected for CAXIII. Positive signals for CAIV and CAXII were observed in the capillary endothelial cells and the basolateral plasma membrane of the epithelial cells, respectively. This study provides an expression profile of all CAs in the mouse harderian gland. These results should improve our understanding of the distribution of CA isozymes and their potential roles in the function of harderian gland. The high expression of mitochondrial CAVB at both mRNA and protein levels suggests a role in lipid synthesis, a key physiological process of the harderian gland.

Retinal very long-chain PUFAs: new insights from studies on ELOVL4 protein

Compared with other mammalian tissues, retina is highly enriched in PUFA. Long-chain PUFA (LC-PUFA; C18-C24) are essential FAs that are enriched in the retina and are necessary for maintenance of normal retinal development and function. The retina, brain, and sperm also contain very LC-PUFA (VLC-PUFA; >C24). Although VLC-PUFA were discovered more than two decades ago, very little is known about their biosynthesis and functional roles in the retina. This is due mainly to intrinsic difficulties associated with working on these unusually long polyunsaturated hydrocarbon chains and their existence in small amounts. Recent studies on the FA elongase elongation of very long chain fatty acids-4 (ELOVL4) protein, however, suggest that VLC-PUFA probably play some uniquely important roles in the retina as well as the other tissues. Mutations in the ELOVL4 gene are found in patients with autosomal dominant Stargardt disease. Here, we review the recent literature on VLC-PUFA with special emphasis on the elongases responsible for their synthesis. We focus on a novel elongase, ELOVL4, involved in the synthesis of VLC-PUFA, and the importance of these FAs in maintaining the structural and functional integrity of retinal photoreceptors.

Breast cancer resistance protein (Bcrp1/Abcg2) is expressed in the harderian gland and mediates transport of conjugated protoporphyrin IX

Proper regulation of intracellular levels of protoporphyrin IX (PPIX), the direct precursor of heme, is important for cell survival. A deficiency in ferrochelatase, which mediates the final step in heme biosynthesis, leads to erythropoietic protoporphyria (EPP), a photosensitivity syndrome caused by the accumulation of PPIX in the skin. We have previously shown that mice with a deficiency in the ABC transporter Bcrp1/Abcg2 display a novel type of protoporphyria. This protoporphyria is mild compared with ferrochelatase-dependent EPP, and in itself not sufficient to cause phototoxicity, but it might exacerbate the consequences of other porphyrias. In this study, we identified the mouse harderian gland as a novel expression site of Bcrp1. Because of its pronounced role in porphyrin secretion, the harderian gland presents a useful tool to study the mechanism of Bcrp1-related protoporphyria and transport of porphyrins. Bcrp1(-/-) harderian gland displayed a highly increased accumulation of PPIX glycoconjugates, and a similar shift was seen in Bcrp1(-/-) liver. Tear- and hepatobiliary excretion data suggest that Bcrp1 controls intracellular levels of PPIX by mediating high affinity transport of its glycoconjugates and possibly low-affinity transport of unconjugated PPIX. This mechanism may allow cells to prevent or reduce cytotoxicity of PPIX under excess conditions, without spillage under physiological conditions where PPIX is needed.

Altered phosphorylation of cytoskeletal proteins in mutant protein phosphatase 2A transgenic mice

Protein phosphatase 2A (PP2A) is a family of heterotrimeric enzymes with diverse functions under physiologic and pathologic conditions such as Alzheimer’s disease. All PP2A holoenzymes have in common a catalytic subunit C and a structural scaffolding subunit A. These core subunits assemble with various regulatory B subunits to form heterotrimers with distinct functions in the cell. Substrate specificity of PP2A in vitro is determined by regulatory subunits with leucine 309 of the catalytic subunit C playing a crucial role in the recruitment of regulatory subunits into the complex. Here we expressed a mutant form of Cα, L309A, in brain and Harderian (lacrimal) gland of transgenic mice. We found an altered recruitment of regulatory subunits into the complex, demonstrating a role for the carboxyterminal leucine of Cα in regulating holoenzyme assembly in vivo. This was associated with an increased phosphorylation of tau in brain and an impaired dephosphorylation of vimentin demonstrating that both cytoskeletal proteins are in vivo substrates of distinct PP2A holoenzyme complexes.

Rapid Induction of Tumors in the Harderian Gland of Mice Receiving Urethane after Initiation with N-ethyl-N-nitrosourea

The rapid induction of hyperplastic foci and adenomas of the Harderian gland by treatment with N-ethyl-N-nitrosourea (ENU) followed by administration of urethane (UR) was studied in male B6C3F1 mice. The mice were initiated intraperitoneally with ENU (40, 60, or 90 mg/kg body wt) once a week for 3 weeks, and given drinking water containing UR (600 ppm) from 1 week after the last exposure to ENU. Light microscopic examination of the Harderian gland was conducted 20, 25, and 30 weeks after the first treatment of ENU to examine sequential changes induced by ENU and/or UR. In mice treated with 40 mg/kg body wt of ENU alone, hyperplastic foci and adenomas were found from week 25, but there were no significant differences in the development of these lesions compared with the vehicle control group until week 30. UR significantly increased the development of ENU (40 mg/kg)-induced hyperplastic foci and adenomas at weeks 25 and 30, respectively, compared with the ENU(40 mg/kg)-alone and UR-alone groups. Magnitudes of initiation by 60 and 90 mg/kg body wt of ENU were too strong to assess the promoting effect of UR. The present results indicate the usefulness of a two-stage system comprising ENU initiation as an in vivo short-term test for carcinogenetic modulators of the mouse Harderian gland.

Effect of Jelly Fish Crude Venom on Liver, Thyroid and Harderian Glands of Female Mice

El-Sawi, N.M. 2002. Effect of jelly fish crude venom on liver, thyroid and Harderian glands of female mice. J. Appl. Anim. Res., 22: 97–104. To study the effect of jelly fish Eutonina indicans crude venom on liver, thyroid and Harderian glands, a sublethal dose was injected i.p. to female mice (1.78 mg/20g body weight). The concentration of porphyrin (μg/100mg) and the levels of serum thyroxine (T4), triiodothyronine (T3) and thyrotropic hormone (TSH) were determined. Histology of tissues from Harderian and thyroid gland were performed. The data indicate that the crude venom induced a highly significant increase (p>0.001) of porphyrin concentration, T3, T4 and TSH levels as compared with those of the control animal due probably to bradykinin which stimulates the synthesis or release of growth hormone or through the activation of prostaglandin synthesis and the thyroid hormones that act directly on Harderian gland. Also lipid peroxides (LPO), total thiols, glutathione, superoxide dismutase and catalase were assayed in liver homogenate and showed alterations of free radicals and antioxidants. The results suggest that this extract may be effective in elevation of T3 and T4 levels in the hypothyrodism patients.

Effect of hyperprolactinemia induced by pituitary grafts or castration on porphyrin content of the mouse Harderian gland.

The histology and porphyrin concentrations of Harderian glands and plasma prolactin levels were examined in B6C3F1 mice castrated or isografted with pituitaries in combination with the administration of bromocriptine (2-bromo-á-ergocryptine), a potent suppressor of prolactin. Four pituitaries were transplanted underneath the bilateral kidney capsules of each mouse. Furthermore, we investigated Harderian porphyrins and plasma testosterone levels in mice that were castrated or treated with neuroleptic butyrophenone (timiperone), a potent accelerator of prolactin, and treated concurrently with bromocriptine. Light microscopically, pituitary grafts increased the concretion of porphyrin pigments within the Harderian gland lumina. Pituitary grafts or castration increased both Harderian porphyrin concentrations and plasma prolactin levels compared with the intact control mice. In pituitary-grafted or castrated mice, bromocriptine distinctly prevented the rise in both porphyrins and prolactin levels. Administration of butyrophenone did not result in any marked change in testosterone levels, although Harderian gland porphyrins were significantly increased. The present results indicate that in mice prolactin stimulates the porphyrin production of the Harderian gland and has an important role in the regulation of Harderian gland porphyrins.

Effects of chronic administration of cytidine-5'-diphosphate choline (CDP choline) on the aged female mouse Harderian gland.

The effect of chronic intake of cytidine-5'-diphosphate choline (CDP choline), a precursor of the membrane lipid phosphatidylcholine, was analyzed in secretory cells of the Harderian gland (HG) of aged (26-month-old) female Swiss mice. These mice were treated with the drug from 12 months of age until they were 26 months old. The results obtained were compared with those of an age-matched control group and another adult (12-month-old) control group. In both control groups, the HGs displayed secretory tubules formed by a single squamous epithelium of lipid-secreting cells. The tubule lumens were occupied by numerous small pleomorphic porphyrin accretions. In contrast, the tubules of the CDP-choline-treated animals consisted of a single columnar epithelium, with lipid-secreting cells filled with lipid vacuoles. The most striking feature in the HGs of the CDP-choline group was the absence of prophyrin deposits. These observations indicate that porphyrin biosynthesis in female Swiss mice is maintained even in very old animals, and that chronic administration of CDP choline prevents porphyrin deposition in the HG of aged animals.

Effect of hyperprolactinemia induced by neuroleptic agent, timiperone, on porphyrin content of mouse harderian gland.

The histology and porphyrin content of the Harderian gland and the serum prolactin levels were examined in male B6C3F1 mice treated with neuroleptic butyrophenones (timiperone and haloperidol) and treated concurrently with timiperone and 2-bromo-alpha-ergocryptine (bromocriptine), a potent suppressor of prolactin. Light-microscopically, both timiperone and haloperidol increased the number of accretions of porphyrin pigment within the Harderian gland lumina. Timiperone treatment of mice increased both the porphyrin content of the Harderian gland and the serum prolactin levels. Administration of bromocriptine to timiperone-treated mice distinctly prevented the rise in both tissue porphyrin and serum prolactin levels. In intact mice, bromocriptine also exerted inhibitory effects on both the Harderian gland porphyrin content and the serum prolactin level. Electron microscopic investigation revealed that the cytoplasm of type A cells in the Harderian glands of mice treated with timiperone contained trilaminar profiles similar to those seen in the intraluminar pigment masses. These results indicate that timiperone accelerates porphyrin secretion from the type A cells of the mouse Harderian gland by increasing the serum prolactin levels.

The harderian gland in autoimmune diabetes of the nonobese diabetic mouse.

Infiltration of the nonobese diabetic (NOD) mouse's Harderian gland (HG) was studied in 1-30-week-old animals. A mononuclear cell invasion of this gland is first seen in 8-week-old female mice (i.e., at a slightly later age than that for the onset of infiltration of pancreatic islets). Infiltrating elements are mainly located at the hilus of the gland or at one or two foci (periacinar infiltration) within the parenchyma. In the latter case, a few elements infiltrate the fibrous connective tissue surrounding the acini (one or more) without damaging them. The most severe histopathological lesion was observed in 16-week-old animals; at this time infiltration ranges from a still focal lesion to complete acinar destruction of the gland. Ultrastructural observations confirm that in several cases acinar cells are destroyed and the HG parenchyma is substituted with infiltrating elements, fibroblasts, and connective tissue. HG infiltration is comparable to the pancreatic inflammatory infiltration; the two processes are very similar, though insulitis starts slightly earlier than HG infiltration. Furthermore, as for insulitis and diabetes incidence, HG infiltration affects NOD males less than females. Moreover, immunocytochemistry has shown that T lymphocytes are the prevalent infiltrating element both in pancreatic islets and HGs. Further studies are required to understand the reasons for autoimmune destruction of this gland.

Protein kinase C isoenzymes in mouse Harderian gland. Differential expression of the ?- and ?-isoforms during pregnancy

Protein kinase C (PKC) is known to be involved in the regulation of exocytosis in different cell lines and tissues. Experiments were designed to determine whether the Harderian gland of CD-1 mouse produces PKC isoenzymes and whether the expression of the isoforms changes during pregnancy. The presence of the isoenzymes was assessed by immunoblotting experiments using extract of total Harderian gland and polyclonal antisera specific for nine different PKC isoforms. Antisera giving a positive staining on Western blots were subsequently used for immunohistochemical investigation using a secondary antibody conjugated to alkaline phosphatase. Immunoblotting experiments revealed that the Harderian gland from female mouse expresses PKC isoforms-α,-e,-ζ and-η. These isoforms were also detected in the Harderian gland from 13-day pregnant mouse; however, striking quantitative changes were seen concerning the α- and e-isoforms. The 80-kDa native form of PKC-α almost doubled in the pregnant mouse in comparison with normal female mouse whereas the amount of 50-kDa catalytic domain did not change. Protein kinase C-e appeared as a 92- to 93-kDa form and a 67-kDa form. While the 92- to 93-kDa protein was expressed to a similar extent in both types of mouse, the 67-kDa form was more abundant inthe Harderian gland from normal female mouse. These data were corroborated by immunohistochemical experiments and showing a diffuse and granular staining of the adenomeres. These observations demonstrate for the first time (to our knowledge) that the mouse Harderian gland produces several PKC isoenzymes that could be involved in the regulation of exocytosis and/or other functions. Moreover, the expression of the α- and e-isoforms could be regulated by sexual hormones, as suggested by the differential abundance of these two proteins in the gland of pregnant mouse compared with normal female mouse.

An initiation-promotion model of tumour prevalence from high-charge and energy radiations

A repair/misrepair kinetic model for multiple radiation-induced lesions (mutation inactivation) is coupled to a two-mutation model of initiation-promotion in tissue to provide a parametric description of tumour prevalence in the mouse Harderian gland from high-energy and charge radiations. Track-structure effects are considered using an action-cross section model. Dose-response curves are described for gamma rays and relativistic ions, and good agreement with experiment is found. The effects of nuclear fragmentation are also considered for high-energy proton and alpha-particle exposures. The model described provides a parametric description of age-dependent cancer induction for a wide range of radiation fields. Radiosensitivity parameters found in the model for an initiation mutation ( sigma 0=7.6*10-10 cm2 and D0=148.0 Gy) are somewhat different than previously observed for neoplastic transformation of C3H10Tl/2 cell cultures ( sigma 0=0.7*10-10 cm2 and D0=117.0 Gy). The authors consider the two hypotheses that radiation acts solely as an initiator or as both initiator and promoter and make model calculations for fractionation exposures from gamma rays and relativistic Fe ions. For fractionated Fe exposures, an inverse-dose-rate effect is provided by a promotion hypothesis with an increase of 30% or more, dependent on the dose level and fractionation schedule, using a mutation rate for promotion similar to that of single-gene mutations.

Fluence-based relative biological effectiveness for charged particle carcinogenesis in mouse Harderian gland

Neoplasia in the rodent Harderian gland has been used to determine the carcinogenic potential of irradiation by HZE particles. Ions from protons to lanthanum at energies up to 670 MeV/a have been used to irradiate mice, and prevalence of Harderian gland tumors has been measured 16 months after irradiation. The RBE for tumor induction has been expressed as the RBE max, which is the ratio of the initial slopes of the dose vs prevalence curve. The RBE max has been found to be approximately 30 for ions with LET values in excess of 100 keV/μm. Analysis on the basis of fluence as a substitute for dose has shown that on a per particle basis all of the ions with LET values in excess of 100 keV/μm have equal effectiveness. An analysis of the probabilities of ion traversals of the nucleus has shown that for these high stopping powers that a single hit is effective in producing neoplastic transformation.

Histopathology of the Harderian gland of rodents exposed to ELF magnetic fields

The Harderian gland is a possible magnetosensitive organ. The aim of this study was to look at the possible effects on the Harderian gland of mice after exposure to an artificial magnetic field. Sixty 0F1 three-month old female mice were selected for this study. The mice were exposed continuously to an artificial magnetic field of 1 G (10 −4 T) and 50 Hz during a three-month period. The effects were evaluated histologically. The results show, only in the experimental group, non-reversible histopathological lesions with anaplasic foci in 26% of Harderian glands. These lesions also include in situ development of adenocarcinomas. Confidence intervals applied to the statistical studies show 95% and 99% (14.75–41.13 and 11.54–45.72, respectively).