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Uptake and distribution of 4,4'-diacetyl-diphenyl-urea-bis-guanylhydrazone in sensitive and resistant sarcoma 180 cells in vitro

1971; Elsevier BV; Volume: 20; Issue: 1 Linguagem: Inglês

10.1016/0006-2952(71)90474-6

1873-2968

Maire Hakala,

Cancer, Hypoxia, and Metabolism

Abstract Sarcoma 180cells sensitive to 4,4'-diacetyl-diphenyl-urea-bis-guanylhydrazone (DDUG) were compared with a resistant subline (S-180/DDUG) with respect to crossresistance to methylglyoxal-bis-guanylhydrazone (CH 3 G), 2-chloro-4',4″-bis(2-imida-zolin-2-yl)-terephthalanilide (NSC 38280) and vincristine (VCR); they were also compared with respect to the nature and rate of cellular uptake of DDUG and its intracellular distribution and binding. Resistance to DDUG was found to be associated with a reduced rate of uptake of DDUG while the intracellular distribution (65–70 per cent in nuclei and 30 per cent in mitochondria) and the capacity for lipid-associated drug binding was unchanged. The uptake was a rapid passive process leading to extensive intracellular accumulation; it was not affected by CH 3 G or VCR, but was inhibited by NSC 38280 or Janus Green. S-180/DDUG cells were cross-resistant to NSC 38280 but sensitive to CH 3 G and VCR, while S-180/VCR cells were cross-resistant to NSC 38280 but sensitive to DDUG and CH3G. In uptake, intracellular distribution and binding DDUG resembles NSC 38280. Combination and cross-resistance studies suggest a lack of similarity between DDUG, NSC 38280, VCR and CH 3 G with respect to the site of growth inhibitory action.