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Teratomas are tumors composed of multiple tissues foreign to the anatomic site from which they originate (Willis, 1951). The term, coined from the Greek words teras meaning monster, and the suffix -oma (from onkoma—swelling) to denote its neoplastic nature, was introduced by Virchow (1863), and since then, it has been used to describe both benign and malignant tumors composed of haphazardly intermixed tissues originating from actually or potentially pluripotent stem cells. Teratomas are considered to be neoplasms because of their progressive, uncoordinated and unregulated growth. The teratoid, ie., monster-like appearance of these tumors, reflects abnormal development of tissues originating from the pluripotent stem cells. Since teratomas represent true neoplasms, most of them are unrelated to congenital malformations or abnormal embryonic development (Warkany, 1971).

Electron microscopy is a valuable morphologic method for the diagnostic evaluation of undifferentiated tumors composed of polygonal or oval large cells and mononuclear or multinucleated giant cells. Although few ultrastructural details are pathognomonic, electron microscopic findings may add significantly to the formulation of the final diagnosis if used in the context of other pathomorphologic and clinical data. Contributions of electron microscopy to tumor diagnosis are summarized and illustrated with appropriate examples from personal experience in a routine university hospital laboratory.

Electron microscopic study of a malignant paraganglioma of the organ of Zuckerkandl revealed similarities between the tumor and the normal paraganglia. The well-differentiated portion of the tumor recapitulated the structure of the basic functional units of the paraganglion. In addition there were signs of anaplasia both at the histologic and ultrastructural level. Large Neurosecretory granules were noted in some of the tumor cells, but most of the cells were agranular. Crystaloids resembling those seen in alveolar soft part sarcoma were also noted. The study supports the theory on the common origin and histogenesis of paragangliomas and alveolar soft part sarcomas.

7 day old mouse egg cylinders transplanted under the renal capsule give rise to both teratomas and teratocarcinomas in mice of C3H/H, CBA and A strains. The proportion of benign to malignant tumors is approximately the same in the three strains. In C57BL mice, only an occasional graft examined histologically 2 months after transplantation of the embryo contains undifferentiated embryonal cells and could thus be considered a teratocarcinoma. None of these “teratocarcinomas” in C57BL mice could be retransplanted and thus unequivocally proven to be malignant. C57BL egg cylinders grafted to C57BL × C3H/H F1 hybrids gave rise to numerous teratocarcinomas. It was possible to obtain teratocarcinomas from C57BL egg cylinders grafted to lethally irradiated isogenic hosts salvaged with the bone marrow cells of C57BL × C3H/HF1 hybrids. These tumors were retransplantable in hybrids but not in inbred C57BL recipients. It was concluded that some host related factors, possibly of an immunologic nature, govern and regulate the outgrowth of tumors from mouse egg cylinders and determine whether the grafted embryo will give rise to benign teratomas or teratocarcinomas.

Teratocarcinoma specified antigen SSEA-1, is present on ejaculated sperm, but it is not evident on testicular sperm. We show that SSEA-1 is secreted by the chief cells of the caput epididymis and is then adsorbed to the surface of the spermatozoa during their passage through the epididymis.

We studied the expression of the human c-myc proto-oncogene in normal human colon epithelium by both in situ hybridization and immunohistochemistry. c-myc was found to be expressed uniformly throughout the entire thickness of the colon epithelium. The present findings do not support the contention that the c-myc proto-oncogene is primarily expressed in proliferating intestinal epithelial cell compartments.

The origin of yolk sac carcinoma obtained from rat embryos transplanted to extrauterine sites was traced to the extraembryonic portion of 9-day egg-cylinders. Under appropriate conditions cells of the extraembryonic portion of the egg cylinder differentiate into cells of parietal yolk sac epithelium, continue to proliferate and form retransplantable malignant tumors. Serum concentrations of alpha-fetoprotein were elevated in rats bearing yolk sac carcinomas and in some animals bearing teratomas admixed with yolk sac carcinoma. Possible factors that regulate the survival and proliferation of yolk sac epithelium in extrauterine sites are briefly discussed.

A case of unilateral massive ovarian edema is presented which clinically had been mistaken for an ovarian tumor. Correct diagnosis was only possible on gross and histologic pathological examination. This is a rare entity which should not be confused with neoplastic lesions by both clinicians and pathologists.

A new latex bead technique for measuring the plaque-forming cell (PFC) responses to bacterial antigens is described. This technique has been designed for the study of antigens that cannot be readily coated onto SRBC but may also used for antigens that adsorb onto SRBC as well. Application of the latex based technique for the study of PFC response of hamsters to Treponema reiter antigen is described in detail. Using SIII, an antigen that readily adsorbs to SRBC, we have compared the latex bead technique and the conventional SRBC-PFC technique and found that the latex bead technique is more sensitive than the conventional technique. The technique can be used for direct and indirect PFC assays. Technical details for the optimal performance of the latex bead PFC assay are outlined.

Mouse blastocysts cultured in vitro in rat serum develop through the early somitic stages of embryogenesis at the same rate as embryos cultured in human cord serum. Rat serum can thus be used instead of human cord serum for in vitro culturing of mouse embryos.

The α- l -fucosidase isoenzyme pattern of mouse teratocarcinoma-derived cell lines was analyzed by isoelectric focusing and compared with the pattern of a mammary carcinoma as an example of a malignant somatic cell line. In addition, these isoenzyme patterns were compared with those of normal fetal and adult mouse tissues from an earlier study. In the normal early fetal and placental tissues as well as in embryonal carcinoma and yolk sac carcinoma cells the α- l -fucosidase activity is predominantly associated with basic forms of the enzyme. This embryonic pattern of α- l -fucosidase is characterized by one to three isoelectric forms of the enzyme with p I values ranging from 7 to 9.5 accounting for more than two-thirds of the total activity. In contrast, the mammary carcinoma pattern resembles adult somatic tissues and primarily expresses acidic enzymatic forms (which comprise approximately 80% of total activity). The somatic cell malignancies arising in retransplantable teratocarcinomas show varying isoenzyme patterns. Thus, a malignant fibrous histiocytoma expresses predominantly basic forms of the enzyme, whereas a leiomyosarcoma expresses approximately equal amounts of acidic and basic forms of the enzyme resembling in this respect late fetal or immature neonatal tissues. These findings show that the embryonal carcinoma and yolk sac carcinoma cells of the mouse express the embryonic isoenzyme pattern of α- l -fucosidase in contrast to malignant cells originating in somatic tissue, like mammary carcinoma, which express the adult pattern. Malignancies arising in somatic tissues of teratocarcinomas may retain the embryonic α- l -fucosidase phenotype or show a phenotype corresponding to late fetal or neonatal tissues in normal ontogeny.

Human and mouse embryonal carcinoma (EC) cells lines were compared with several cell lines of a more differentiated phenotype for their relative sensitivities to the cytotoxic effects of cis-platinum (cis-diamine-dichloroplatinum; CDDP); EC lines were among the most sensitive. Furthermore, several markers of EC cell differentiation were not induced by CDDP, irrespective of the concentration of the drug used. These data provide an explanation for the relative sensitivity of the EC cells in non-seminomatous germ-cell tumors to cis-platinum therapy.

Fluorescein isothiocyanate (FITC) labeled lectins were used to study the distribution of specific binding sites in histologic sections of mouse ovaries as well as ovulated ova. Four distinct patterns of reactivity of the components of the follicle (exclusive of the ovum) and the surrounding ovarian stroma were recognized: 1. uniform staining of granulosa cells, theca cells and surrounding stroma; 2. weak to moderate staining of the granulosa cells and strong staining of the theca cells and stromal cells; 3. no reactivity of the granulosa cells coupled with strong reactivity of the theca and stromal cells; 4. no reactivity with any component of thecumulus oophorus. Three lectins (from Triticum vulgare, Arachis hypogaea and Maclura pomifera) distinctly accentuated the basal lamina of thecumulus oophorus. The reaction of lectins with oocytes and zona pellucida revealed six distinct patterns: 1. no reactivity with either structure; 2. weak reactivity with the cytoplasm of the oocyte and no reactivity with the zona pellucida; 3. very strong reactivity with the cytoplasm of the oocyte and no reactivity with the zona pellucida; 4. moderate reactivity with both the oocyte and the zona pellucida; 5. moderate reactivity with the oocyte and very strong reactivity with the zona pellucida; 6. no reactivity with the oocyte and moderate reactivity with the zona pellucida. The same pattern of reactivity was seen in the ovulated ova in the oviduct except for the lectin from Arachis hypogaea, the reactivity of which changed upon ovulation and/or fertilization of the ovum. These data provide a list of lectin markers for distinct components of the mouse ovary.

A case of mullerian adenosarcoma arising in the endometrium was studied by light and electron microscopy before and after radiation treatment. The tumor was composed of malignant stroma containing undifferentiated mesenchymal cells admixed with mature fibroblasts and other cells that contained crystalloids. The surface epithelium was lined by epithelial cells with and without cilia, similar to the normal surface epithelium cells of the uterus. High-dose therapeutic irradiation eliminated the undifferentiated mesenchymal cells from the tumor but did not alter the morphology of other epithelial and mesenchymal elements. The immaturity of mesenchymal cells and their radiosensitivity coupled with the ultrasonographic evidence of growth of the tumor point to the probable malignant nature of this neoplasm.

The fetotoxicity and teratogenicity of metronidazole and ethanol administered alone and together were studied in Swiss Webster mice. We found that both metronidazole and ethanol were mildly fetotoxic and teratogenic when administered alone. However, simultaneous administration of the 2 drugs had an additive effect and resulted in increased fetotoxicity and teratogenicity.

Egg cylinders developed in vitro from explanted mouse blastocysts were transplanted under the kidney capsules of adult mice to assess their developmental potential. In vitro grown egg cylinders are capable of differentiation into somatic tissues and may give rise to stem cells of teratocarcinoma like the developmentally equivalent 7 day mouse embryos grown in vivo.

Six- to 8 1/2-day inbred MHA/SsLak and outbred Syrian golden hamster embryos and 14-day fetal lungs, testes, and portions of small intestine were transplanted into cheek pouches or under kidney capsules of adult recipients. Embryonic grafts gave rise to benign teratomas, irrespective of the age of the embryo, transplantation site, and the strain or stock of recipient. Fetal lung and testis grew little in extrauterine sites, whereas fetal intestine formed large mucus-filled cysts lined with proliferating and apparently functionally active epithelium.

The Bandeiraea simplicifolia lectin I (BSA-I) conjugated to fluorescein isothiocyanate was used as a histochemical reagent to study the mouse embryos from fertilization to early somitogenesis. No lectin binding could be detected on the embryonic cells in the preimplantation embryo. Lectin labeled intensely the zona pellucida. In the implanting embryos lectin binding was detected along the subtrophectodermal and Reichert's membrane, in the cytoplasm of the parietal and visceral endoderm, and the trophoblastic giant cells, but not in the ectodermal cells. Studies on explanted blastocyts cultured in vitro disclosed that the cytoplasmic BSA-I binding sites in trophoblastic cells develop gradually. In the 9-day somitic embryo BSA-I reacted with epithelial cells of the yolk sac, but not with the mesenchymal cells. A continuity between the lectin-reactive endoderm and the foregut epithelium could be demonstrated. These data indicated that BSA-I lectin can be used as a histochemical probe for endodermal (yolk sac) and trophoblastic differentiation in the peri-implantational mouse embryo.

Monoclonal antibodies to cytoskeletal proteins were used to study the intermediate filament proteins of human embryonal carcinoma (EC) cell lines, tumors produced in nude mice from these cell lines, and surgically removed testicular germ cell tumors. It was found that all cells of tumor lines 2102Ep, 1156 and Tera 1 react with antibodies to low molecular weight keratin proteins. By immunoblotting of SDS gels it was found that these lines expressed three keratin polypeptides (40K, 45K and 52K). Clonal line NTera-2 derived from Tera-2 differed from the above listed cell lines in that only 10% of the cells expressed the 40K keratin polypeptide. Upon treatment with retinoic acid 70% of NTera-2 cells became reactive with the antibody to the 40K keratin polypeptide. All cell lines contained a small population of vimentin-positive cells. The number of vimentin-positive cells could be increased by retinoic acid treatment of NTera-2 cells or by seeding the 2102Ep cells at low cell density. Neurofilament-positive cells could be induced in the cell line NTera-2 by retinoic acid treatment. Tumors produced from NTera-2 cells injected into nude mice contained cells reacting with antibodies to keratin, vimentin, neurofilament proteins and desmin. Keratin polypeptides were immuno-histochemically demonstrated in embryonal carcinoma, yolk sac carcinoma and trophoblastic components of solid human germ cell tumors. A typical intratubular cells (‘carcinoma in situ’) also reacted with antibodies to keratin.

A symptomatic myelolipoma of the heterotopic adrenal gland was diagnosed as the cause of nephrotic syndrome and was surgically removed. Remission of the nephrotic syndrome promptly ensued. Ultrastructurally, the tumor consisted of well-differentiated cells resembling adrenal cortical cells, bone marrow cells in various stages of differentiation, and lipid cells. Some cells that contained fat were of adrenal cortical origin, but the derivation of most lipid cells and of bone marrow elements could not be deduced from the present ultrastructural findings.

Summary o 1. In a series of 11 experiments in 10 mongrel dogs, closed chest cardiopulmonary bypass was begun 1 to 35 min after all evidences of cardiorespiratory function had ceased following exsanguination. The animals had been previously heparinized and cannulated. 2. Heart function could be restored after 1 hr of perfusion in seven experiments; in three of five animals with no evidence of cardiorespiratory function for 30 min or more, effective cardiac function returned after resuscitation. Surface pH of the heart rose to above 7 units after 1 hr of perfusion, suggesting relative integrity of the myocardial diphosphopyridine-nucleotide-FPN cytochrome oxidase transport system. 3. From this small series of experiments, it would appear that clinical cadaver perfusion may be carried out 30 or more min after death with some expectation of restoring heart (but not brain) function. 4. It remains to be shown that a heart obtained under these circumstances is indeed transplantable and will maintain long term functional integrity.

Mouse egg-cylinders of C3H/H strain with two and three germ layers were transplanted under the kidney capsule. They developed into well differentiated teratomas and teratocarcinomas. Older embryos developed invariably into teratomas composed of adult tissues only. We consider the period of germ layer inversion as a critical stage when embryonic cells loose their potentiality for uncontrolled growth.

The time of appearance and the distribution of alkaline and acid phosphatase and nonspecific esterase was investigated in cleavage and early postimplantation stages of mouse and rat embryos.

Cell line IgSV195, derived from a pancreatic tumor that arose in an SV40 T-antigen transgenic mouse, retains certain morphological and physiological characteristics of pancreatic beta-cells throughout in vitro and in vivo passage. Insulin secretion is stimulated by exposure of these cells to fetal bovine serum and a combination of 3-isobutyl-1-methylxanthine and glutamine but not by concentrations of glucose in the physiological range. Insulin processing appears to be intact. Neither class I nor class II major histocompatibility complex (MHC) antigens are routinely expressed at the cell surface; however, MHC class I--but not class II--encoded gene products are detected after treatment with recombinant interferon-gamma (IFN-gamma) alone or in combination with tumor necrosis factor. Cytolysis of IgSV195 cells by SV40 T-antigen-specific H-2b-restricted lymphocytes is similarly dependent on IFN-gamma pretreatment. These results emphasize that SV40 T-antigen transgenic mice are likely sources of cell lines that retain their differentiated function in vitro. The IgSV195 cell line provides an accessible model in which to investigate the control of gene expression and function of pancreatic beta-cells.

Cis-diamminedichloroplatinum has lethal, toxic and teratogenic effects on presomitic mouse embryos in doses that are not toxic to adult animals.

A panel of six monoclonal antibodies and a conventional polyclonal antibody raised against human placental alkaline phosphatase (ALP) were used to characterize the alkaline phosphatase detected by means of histochemistry on tumors of breast, ovary, lung, gastrointestinal tract, and kidney. Complete antigenic identity between the tumor ALP and the placental ALP was found only in one lung tumor. However, ten tumors reacted with the polyclonal antibody and some monoclonal antibodies, thus exhibiting partial identity with the placental ALP.

The intermediate-filament proteins of normal, hyperplastic, and adenomatous parathyroid glands were analyzed immunohistochemically and by immunoblotting with monospecific antibodies. In both normal and adenomatous parathyroid glands, we found keratins with molecular weights of 52, 45, and 40 kilodaltons (Nos. 8, 18, and 19, respectively). Vimentin proteins could be identified only in stromal cells, while glial fibrillary acidic protein was not found. In normal parathyroid glands, neurofilament positivity was seen only in nerve axons. In five of 15 parathyroid gland adenomas some keratin-positive cells expressed neurofilamentlike immunoreactivity also. In cytoskeletal extracts of one adenoma, the 200-kilodalton neurofilament protein was identified by immunoblotting. Thus it appears that some parathyroid gland adenoma cells may acquire neurofilament proteins and coexpress cytokeratin and neurofilament polypeptide in a way comparable with that reported in certain neuroendocrine tumors.

A 26-year-old black man presented with gross hematuria and was found to have a papillary lesion of the trigone of the bladder. The lesion proved to be an adenomatous polyp with prostatic-type epithelium. This type of neoplasia ordinarily is found in the prostatic urethra and has not been reported previously in the bladder. Adenomatous polyps are benign tumors and should be considered in the differential diagnosis of hematuria in young men.

A significant aspect of primary hepatic carcinoma in man is the high positive correlation of hepatocellular carcinoma with infection with hepatitis B virus (HBV)1. Analysis of the relationship between HBV infection and oncogenesis is difficult because natural infection with HBV is limited to man and experimental infection has been achieved only in chimpanzees and gibbons. Furthermore, because HBV has not been successfully propagated in cell culture, basic study of virus-cell interaction of the aetiological agent of one of the most widespread infections of man has been impossible. Recently, however, a cell line (PLC/PRF/5) derived from a human hepatoma biopsy was described which produces the HRV surface antigen (HBsAg) and so provides a tool for the experimental investigation of HBV in viro. We now report the derivation and characterisation of two additional cell lines primary liver carcinomas. In contrast to the PLC/PRF/5 cell line, these cell lines retain the capacity to synthesise many human plasma proteins, including both albumin and alpha-fetoprotein (AFP). One of these lines also produces BHsAg. We also present evidence that HBsAg synthesis and secretion in this cell line are correlated with the growth state of the culture. This finding is in contrast to the continuous HBsAg production found in the PLC/PRF/5 cell line.

WHEN Stevens transplanted mouse ova at the one and two cell stage into the testis of a 129/Sv mouse, teratomas consisting of several types of differentiated and undifferentiated tissues resulted1. Tumours developed only when transplantation was into the 129/Sv-SlJCP strain, known for developing frequent spontaneous testicular teratomas. In other strains of mice, Stevens1 obtained no growth of tubal ova after transplantation into the testis. Kirby2 obtained only trophoblast and extraembryonic derivates after grafting tubal eggs under the kidney capsule and in the testis, but when he grafted blastocysts the egg-cylinder developed. Similar results were reported3–6, but the experimental period was too short (up to 15 days) for histogenesis. Nicholas7 reported histogenesis after the transfer of tubal eggs under the kidney capsule, but his experiments have never been repeated successfully. Histogenesis and full differentiation are probably stopped by trophoblastic overgrowth5,6. Grobstein8 and Levak-Svajger and N. S.9 found fully differentiated adult tissues in rat egg-cylinder grafts maintained for 30 days in the anterior chamber of the eye. They found no evidence of atypical or malignant cells.

Summary Precocious puberty with signs of masculinization and elevation of choriogonadotrophic activity in a girl 7½ years old was found to be due to a hormonally active ovarian tumour. The tumour was composed of germ cells, Leydig cells, Sertoli granulosa-like cells, trophoblastic and teratoid portions, and was therefore, termed a terato-chorio-gonadoblastoma. Hormonal data were correlated with the histological and ultrastructural findings. This unusual tumour caused precocious puberty coupled with virilization and high choriogonadotrophic activity in a girl 7½ years old.

T HE EXISTENCE of branchial cleft carcinoma is not unanimously accepted although Volkmann 1 in 1882 proposed this concept of origin for a certain number of carcinomas arising in the lateral aspects of the neck. Reviewing 250 cases published in the world literature until 1950, Martin et al 2 concluded that none of these cases were properly documented as to origin, and proceeded to establish criteria for proper diagnosis of branchial cleft carcinoma. Since then, eight cases, 3-8 all with apparently acceptable evidence of branchial origin, have been reported, although a complete postmortem examination was not done at the termination of any of these cases. Because there are still controversies concerning the existence of a carcinoma arising in the wall of a branchial cleft cyst, the autopsy findings in the following case are presented. Report of a Case A 59-year-old white man had a huge cervical mass in the left

Polyclonal antisera against rat visceral yolk sac (VYS) produces severe congenital malformations when injected into pregnant rats on the 9th day of gestation. To define and characterize the teratogen-stimulating antigen(s) from the VYS, monoclonal antibodies (MCA) against rat VYS were prepared. Spleen cells from BALB/c mice, hyperimmunized with VYS antigens purified by IEF and gel filtration were fused with two myeloma cell lines SP2/0-Ag 14 and P3x63 Ag. 8.653. Hybrids specific for VYS by indirect immunofluorescence were selected and cloned by limiting dilution and further expanded as ascitic tumor in BALB/c mice. More than 25 immunofluorescent hybrids for VYS have been selected and their biological activity defined. The first 12 clones were not teratogenic but since last year (1986) ascitic fluid from B-3 clone (IgG 2b type) induced CNS malformations and the clone D-4 (IgG 2a type) induced growtn retardations when injected into pregnant rats on the 9th day of gestation. Each teratogenic MCA stained the apical portion of VYS endodermal cell, tubular kidney brush border and failed to react with kidney glomeruli, Reicherts membrane, long, lens capsule and liver tissue by immunofluorescence. Both teratogenic MCA's failed to recognize the VYS antigens by Western blots. Further studies will be directed toward using the teratogenic MAC's to study the mechanism of teratogenesis and the quantitative aspects of embryonic nutrition during early organogenesis. (Supported by NIH)

To the Editor.— Only roughly a third of all the graduates of the University of Zagreb School of Medicine (UZSM) who take the examination given by the Educational Council for Foreign Medical Graduates (ECFMG) score the 75 or more needed to pass the examination. We have analyzed some of the possible reasons in 103 Yugoslav graduates of our medical school who took the ECFMG examination in 1967 or 1970. The list was compiled from records sent biannually to the Dean of UZSM. Foreign graduates were eliminated. The university records of the Yugoslav graduates were analyzed. Data on 1,342 other students who graduated in 1967 or 1970 served for comparison. The analyzed group consisted of 30 women and 73 men, 24 to 47 years of age. The mean interval between graduation and first examination was 6.7 years (range, 0 to 19). We compared the average grades of those taking the ECFMG

To the Editor.— The article by Herron et al (242:53, 1979) reports convincingly the safety and efficacy of influenza vaccination in patients with various immunologically mediated diseases. Since there are no major complications of recent influenza vaccination on record, we want to report our experience with a patient with Henoch-Schonlein purpura, whose mild renal disease progressed irreversibly after influenza vaccination. Report of a Case.— A 23-year-old man with a ten-year history of Henoch-Schonlein purpura was hospitalized in November 1976, three weeks after vaccination with the whole bivalent influenza virus vaccine (A/NJ and A/Vict). The symptoms included fever, abdominal colics, gross hematuria, joint pains, and skin purpura. The blood pressure reading was 160/100 mm Hg. Stools were positive for blood, and the urine contained blood and RBC casts. The serum protein level was 4 g/24 hr. The level of serum BUN was 43 mg/dL; creatinine, 3.3 mg/dL; and creatinine clearance, 36

Twenty fluorescein isothiocyanate-labeled lectins were applied to formalin-fixed, paraffin-embedded sections of rat spinal cord to delineate the specific lectin binding sites on the ependymal cells. Only two lectins, Solanum tuberosum agglutinin (STA) and wheat germ agglutinin (WGA), were found to bind intensely to the ciliated surface of rat ependymal cells. Inhibition studies indicated that terminal N-acetylglucosamine and sialic acid were abundantly present on the ciliated surface of ependymal cells and accounted for the binding of these two lectins. Experimentally induced hydromyelia was accompanied by a loss of lectin binding sites on the ependymal cells. These data show that STA and WGA represent potentially valuable new histochemical markers for ciliated ependymal cells.

To the Editor.— Concerning the recent question about the safety of metronidazole use in pregnancy, 1 I would like to add a note of caution based on our experimental data. As correctly pointed out by Dr Friedrich, who answered the letter to JAMA , there are no reports on the teratogenicity of metronidazole in humans. For all practical purposes metronidazole is not teratogenic in experimental animals, 2 unless administered in extremely high doses. However, if metronidazole together with ethyl alcohol is given to pregnant mice, fetotoxicity and teratogenicity occur far in excess of that noted in animals exposed to each of these drugs administered separately. 2 It seems that, in mice, metronidazole potentiates the teratogenicity of alcohol. Since metronidazole may cause intolerance to alcohol 3 as well as dizziness and nausea if taken together with alcohol, a warning against the simultaneous use of two drugs in pregnancy may be warranted.