Moloney sarcoma virus

PMEA and its congeners are more effective in vivo than could be predicted from their in vitro potency. While less potent as an antiretrovirus agent than AZT in vitro, PMEA proved clearly superior to AZT when the two drugs were compared for their effectiveness in vivo, in mice infected with murine Moloney sarcoma virus [51,52]. PMEA was also shown to be effective against various other retrovirus infections, including Friend leukemia virus (FLV), Rauscher leukemia virus (RLV), and LP-BM5 (murine AIDS) virus infection in mice, feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) infection in cats, and SIV infection in macaque (rhesus) monkeys (for review, see Ref. 53). In the latter model [54], again PMEA proved far superior to AZT in suppressing several parameters of the disease. 

The concentration of toxin which causes a 50% reduction in cell bound dye after five days in culture. Cell lines used were H4TG, thioguanine-resistant rat hepatoma cells MDCK, Madin-Darb and canine kidney cells NIH3T3,NIH Swiss mouse embryo fibroblasts and KA31T, Kirsten strain of Moloney sarcoma virus-transformed 3T3 cells. 

C57 BL/C mice Pb in drinking water, 130-1,300 ppm, chronic exposure Moloney sarcoma virus challenge and tumor development Growth of primary tumors enhanced by Pb dosing Kirkviiet and Boecher-Steppan (1982)... 

Levinson, B., Khoury, G., Van de Woude, G., and Gruss, P., 1982, Activation of SV40 genome by 72-base pair tandem repeats of Moloney sarcoma virus. Nature 295 568-572. 

In vitro studies S of anti-vaccinia activity have been carried out with a series of rifamycin derivatives and with their corresponding aminoplperazine side chains. Several of the side chains per se were claimed to be more active than the rifamycin. These effects could not be demonstrated by other workers. It was shown by plaque assays and by morphological changes in cells, that the side-chain of rifampicin had no effect on the course of virus Infection. Several mechanisms of antiviral action have been proposed for rifamycin derivatives but the greatest interest centers around the inhibition of RNA-directed DNA polymerase. Several rifamycin derivatives but not rifampicin itself exhibit greater than 50% inhibition of the RNA-directed DNA polymerase of Moloney sarcoma virus (MSV) at concentrations of 50-100 mcg/ml. 

BCG has also been studied in several experimental models. Maximum tumor inhibition and prevention of pulmonary metastases in animals with methylcholanthrene sarcoma followed BCG plus live tumor vaccine inoculated intralesionally. 6,47 Bansal and Sjogren have shown that BCG must be given before the tumor reaches a critical size otherwise BCG enhances the blocking effects on the enlarging tumor.Finally BCG decreases the tumor size in Moloney sarcoma virus Infected mice which had been immunosup-pressed by cytoxan. Analysis of the guinea pig hepatoma model revealed that both the BCG cell wall suspension in oil and isolated BCG cell wall components were as effective as the live organisms.50 Another BCG product, methanol-extraction residue (MER) has also been extensively studied and shown to stimulate a positive host response towards tumor rejection.51... 

Viral Action at the Level of Translation. It is known that in eukaryotic cells induction and repression of enzyme synthesis can occur at the level of messenger RNA (Tomkins and Martin, 1970). Thus, the SV40, polyoma, and Moloney sarcoma viruses could contain the genetic information for a common repressor molecule which could interfere with the synthesis of aminosugar transferase. Both DNA viruses can code for 5-10 polypeptides (Eckhart, 1969), and the potential coding capacity of the large RNA tumor viruses is extensive. 

Balzarini J, Sobis H, Naesens L, Vandeputte M, De Clercq E. Inhibitory effects of 9-(2-phosphonylmethoxyethyl)adenine and 3 -azido-2, 3 -dideoxy-thymidinc on tumor development in mice inoculated intracerebrally with Moloney murine sarcoma virus. Int J Cancer 1990 45 486-489. 

Papkoff, J., Verma, I. M., and Hunter, T. (1982). Detection of a transforming gene product in cells transformed by Moloney murine sarcoma virus. Cell 29 417-426. 

Numerous structural modification studies of ellipticine have been conducted. It is found that side-chain substitution has considerable influence on the biological activity to compounds of this type. A pyridopyrrolo[2,3-g]iso-quinoline derivative, BD-40 (48) [235, 236], has demonstrated potent activity against many different experimental tumours including leukaemia L1210 and the Friend virus leukaemia. It is also active against the Moloney strain of murine sarcoma virus [237]. Phase I clinical study of (48) has been conducted [238, 239]. 

Polymer (VI) has been shown to have antitumor activity against adenocarcinoma 755, Dunning ascites leukemia. Friend leukemia virus, and Lewis lung carcinoma. In the latter case, polymer (VI) showed activity about equal to that of cyclophosphamide (an alkylating agent) and was more effective than 6-mercaptopurine (an antimetabolite) ( ). The DIVEMA polymer (V) Is also active against some cancer causing viruses such as Friend leukemia, Moloney sarcoma and Rauscher leukemia ( ). 

The individual (/ ) and (5) enantiomers of 2-phosphonomethoxypropyl (PMP), 3-hydroxy-2-phosphonomethoxypropyl (HPMP) and 3-fluoro-2-phosphonomethoxypropyl (FPMP) derivatives (44) and (45) of adenine, 2-aminopurine, 2, 6-diaminopurine, and guanine have been prepared and tested against HIV and Moloney murine sarcoma virus (MSV). Of these (/ )-PMPDAP emerged as the most potent and selective in vitro and in vivo antiretroviral agent reported so far. 

Spandidos, D. A., and Wilkie, N. M., 1983, Host specificities of papillomavirus, Moloney murine sarcoma virus, and SV40 enhancer sequences, EMBOJ. 2 1193-1199. 

An efficient method for the synthesis of both (R)- and (5)-enantiomers N -[3-fluoro-2-(phosphonomethoxy)propyl] derivatives (822) of the purine bases adenine and 2,6-diaminopurine (FPMPDAP), has been developed by Janeba et al. Whereas none of (822) showed any antiviral activity, several FPMPDAP derivatives (R = cyclopropyl) had a moderate antiretroviral anti-HIV/MSV(anti-human immunodeficiency virus (FIIV) and anti-Moloney murine sarcoma virus (MSV)) activity. ... 

DNA = deoxyribonucleic acid MLV = Moloney mouse sarcoma-1eukemia virus RLV =... 

In the mouse the Moloney retrovirus is fully mature, enveloped, and induces lymphocytic leukemia. Deprived of its envelope, the Moloney retrovirus induces soft tissue sarcomas, the most dominant of these tumors being the rhabdomyosarcoma [1806a, b, 1807a, b]. In tissue cultures, murine leukemogenic viruses lose... 

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