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Why Is Tumor tRNA Hypomodified with Respect to Q Nucleoside?

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Modified Nucleosides and Cancer

Abstract

Nucleoside Q is found exclusively in the first position of the anticodon in tRNATyr, tRNAHis, tRNAAsn, and tRNAAsp (Kasai et al. 1975b, 1976). Its function is unknown, and long-term Q-deficient, germ-free mice appear normal (Reyniers et al. 1981). However, queuirie metabolism is altered in neoplasia. Many tumors exhibit Q-deficient tRNA (Katze 1975; Okada et al. 1978; Roe et al. 1979) and queuine addition to tumor-bearing mice can reverse tumor tRNA Q deficiency (Katze and Beck 1980; Nishimura et al., this volume pp. 401–412) and may inhibit tumor growth (Katze and Beck 1980). It is unlikely that Q-deficient tRNA is necessary for the neoplastic state since the careful study of Marini and Mushinski (1979; Mushinski and Marini, this volume pp. 121–132) shows widely varying, repeatable isoaccepting patterns (largely due to differences in Q content) for the Q family of tRNAs from several Balb/c mouse plasmacytomas with similar growth rates and size at harvest. These large differences among such a similar group of tumors suggest that the alteration in Q metabolism is secondary to the neoplastic process.

This work was supported by grants from the National Institutes of Health, CA-23099 and CA-21765 (W.T.B.), CA-20919 (J.R.K.), GM-29812 (J.A.M.); and ALSAC (W.T.B.). We thank P. Moore for her excellent assistance

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Abbreviations

Q or nucleoside Q or queuosine:

7-(4,5-cis-dihydroxy-l-cyclopenten-3-ylaminomethyl)-7-deaza-guanosine

Q base or queuine:

the aglycone of queuosine

[Q+]tRNA:

tRNA containing Q in the first position of the anticodon

[Q-]tRNA:

the unmodified or precursor form of [Q+]tRNA containing guanosine instead of Q in the first position of the anticodon

rQD3 :

the reduced and deuterated derivative of queuine (see text)

rQT3 :

the reduced and tritiated derivative of queuine (see text)

8azaG:

8-azaguanine

FBS:

fetal bovine serum

[Q-]FBS:

FBS treated with charcoal plus dextran to remove queuine (Katze, 1978b)

HPLC:

high-performance liquid chromatography

HEPES:

N-2-hydroxyethylpiperazine-N′-2ethane sulfonic acid

Tricine:

N-Tris(hydroxymethyl)methyl glycine

A260 unit:

the amount of material giving an absorbance of 1.0 at 260 nm when dissolved in 1 ml of water and measured in a cell of a 1-cm light path. In this study, Q is used generically to designate Q, and Q* denotes queuosine containing galactose or mannose bound to carbon 4 of the cyclopentenediol substituent.

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Katze, J.R., Beck, W.T., Cheng, C.S., McCloskey, J.A. (1983). Why Is Tumor tRNA Hypomodified with Respect to Q Nucleoside?. In: Nass, G. (eds) Modified Nucleosides and Cancer. Recent Results in Cancer Research/Fortschritte der Krebsforschung/Progrès dans les recherches sur Ie cancer, vol 84. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-81947-6_10

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  • DOI: https://doi.org/10.1007/978-3-642-81947-6_10

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