The Presence of Oncofetal Antigens on Ultraviolet Light-Induced and Methylcholanthrene-lnduced Murine Tumors Which Are Common to Placental and Fetal Tissues*

ABSTRACT: Previous studies employing ultraviolet light-induced (UV-induced) and methylcholanthrene-induced (MCA-induced) tumors have elucidated the presence of three functionally denned groups of tumor antigens. One is the tumor-specific transplantation antigens (TSTA), which represent the most potent tumor-rejection antigens. The second is the tumor-associated transplantation antigens (TATA), which appears to be etiology-dependent (ultraviolet light-UV-or methylcholanthrene-MCA) and is capable of acting as a rejection antigen following hyperimmunization. The third is the tumor-associated antigens (TAA) which, to date, has only been defined by in vitro assays. The TAA appear to be present on all murine tumors tested. We feel that the TAA are functionally related to fetal antigens. In these experiments, cytotoxic T lymphocytes (CTL) generated from the popliteal lymph nodes of C3H mice immunized with a C3H, UV-induced tumor (RD-1024) were capable of causing specific lysis of not only the immunizing tumor but also of fetal fibroblasts (FFB) and placental cells (PC) obtained from syngeneic C3H × C3H matings. In cold-cell inhibition experiments, unlabeled placental cells could abolish specific lysis of labeled placental cell targets, fetal fibroblast targets, and secondary tumor targets (LR80, a MCA-induced tumor) while not inhibiting lysis of the immunizing tumor. Placental cells and fetal fibroblasts from 12-day to 14-day syngeneic C3H pregnancies were capable of eliciting a CTL response by footpad immunization of virgin C3H female mice. Anti-FFB or anti-PC CTL were capable of killing all tumors tested (UV-induced or MCA-induced) and were without H-2 restriction as demonstrated by specific lysis of a BALB/c tumor. These results indicate that antigenic determinants present on 12-day to 14-day fetal and placental cells satisfy the functional definition of the TAA.     

Studies on Reproduction in Rats with Meclofenamate Sodium, a Nonsteroidal Anti-inflammatory Agent

Studies on Reproduction in Rats with Meclofenamate Sodium, aNonsteroidal Anti-inflammatory Agent. PETRERE, J. A., HUMPHREY,R. R., ANDERSON, J. A., FITZGERALD, J. E., AND DE LA IGLESIA,F. A. (1985). Fundam. Appl. Toxicol. 5, 665–671. Reproductionand teratology studies were performed in rats given meclofenamatesodium, a nonsteroidal anti-inflammatory agent. Dosages of 0,3, 6, and 9 mg/kg were administered orally as dietary admixturesin the Fertility and Perinatal-Postnatal studies. In the Teratologystudy, dosages of 10, 12, 15, and 20 mg/kg were administeredby intragastric intubation. In the Male-Fertility study no adverseeffects on fertility or litter and offspring parameters wereobserved in two generations. In the Female-Fertility and Perinatal-Postnatalstudies, maternal toxicity (death associated with intestinalulceration and adhesions) was particularly evident during lactation.Prolonged gestation periods, decreased weanling weights, andincreased weanling mortality were evident at dosages of 6 and9 mg/kg. Increased postimplantation loss occurred at 6 and 9mg/kg in the Term Sacrifice subgroup of the Female-Fertilitystudy. Fertility rates were unaffected and all other litterand offspring parameters of the F₁ and F₂ generations appearednormal. In the Teratology study no adverse effects on embryonicor fetal development were evident at maternally toxic dosagesup to 20 mg/kg. © 1985 Society of Texicology.     

Aminoglycoside-Induced Biphasic Hindlimb Paralysis in the Rat: A Histological and Electrophysiological Assessment

Aminoglycoside-Induced Biphasic Hindlimb Paralysis in the Rat:A Histological and Electro-physiological Assessment. TOLLIVER,J. M., AND WARNICK, J. E. (1985). Fundam. Appl. Toxicol.. 5,933-947.The intrathecal injection of gentamicin into a human patientwith gram-negative bacterial meningitis as well as its intracisternalinjection into rabbits caused spongy-like lesions in the graymatter and tetraplegia in rabbits. To characterize this neurotoxiceffect, gentamicin was injected into the subarachnoid spaceof the lumbar spinal cord of the rat. A biphasic hindlimb paralysisensued which consisted at first of a transient flaccid paralysislasting 1 to 5 hr followed by a permanent flaccid paralysiswhich developed after 24 to 36 hr. The initial paralysis occurredsimultaneously with the transient loss of reflex transmissionthrough the cord but in the absence of lesions in the spinalcord or physiological alterations of neuromuscular transmissionand muscle contraction. The onset of the second phase of paralysisoccurred concomitant with changes in reflex transmission andappearance of lesions. Loss of neuromuscular transmission andappearance of signs of denervation (e.g., depolarization, alterationin action potential parameters, and chemosensitivity) appearedafter the second phase of paralysis was established Both theinitial transient and late permanent paralysis originated inthe spinal cord. The early transient paralysis appears to bedue to a central block of transmission while the late paralysisapparently resulted from neuronal damage. The neurotoxic effectsof aminoglycosides on neuronal elements in the spinal cord resultedin secondary effects (signs of denervation) in hindlimb muscles.