In vivo generation and selection of variants with altered sensitivity to natural resistance (NR): a model of tumor progression.

Abstract:

:The stability of a cloned murine tumor for sensitivity to NR was examined following growth in vivo in order to test the hypothesis that tumor progression proceeds through the generation and selection of variants. Clonal sensitivity to the [131I]-dUrd elimination assay of NR was assessed for the L5178Y-F9 tumor grown in syngeneic DBA/2 mice or maintained solely in tissue culture. Subclones derived from a tumor obtained from the injection site 3 1/2 weeks after the s.c. inoculation of 25 cells were less sensitive to NR in comparison with subclones derived from cells grown only in vitro. Subclones from the cells grown in vivo exhibited increased heterogeneity in sensitivity to NR in addition to their expanded range of susceptibility to complement-mediated lysis by CBA serum natural antibodies. The extent of the heterogeneity argues against tumor "adaptation" forming the basis for the phenotypic alteration while chromosomal studies eliminate the possibility that a new tumor was induced. These data support the hypothesis that tumor progression proceeds through the random generation of variants and host-mediated selection for the proliferation of clones with an increased ability to survive.

journal_name

Int J Cancer

authors

Chow DA,Ray M,Greenberg AH

doi

10.1002/ijc.2910310116

subject

Has Abstract

pub_date

1983-01-15 00:00:00

pages

99-105

issue

1

eissn

0020-7136

issn

1097-0215

journal_volume

31

pub_type

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