In vitro cytotoxicity of tetracyclines and aminoglycosides in LLC-PK(1), MDCK and Chang continuous cell lines.

ABSTRACT

The objective of this study was to determine if cell lines isolated from particular organs retain their sensitivity to xenobiotic toxicity in vitro. The toxicity of chlortetracycline, demeclocycline and tetracycline was examined in the proximal kidney (LLC-PK(1)), distal kidney (MDCK) and human liver (Chang) cell lines. The toxicity of amikacin, gentamicin and neomycin was studied in the LLC-PK(1) and MDCK lines. Cytotoxicity was assessed by cytoplasmic LDH leakage. Kidney cells treated with tetracyclines displayed minimal toxic response. The Chang cell line showed greater sensitivity to these compounds and ranked them as follows demeclocycline > chlortetracycline > tetracycline. The kidney lines produced the rankings as follows LLC-PK(1) amikacin > neomycin > gentamicin; MDCK neomycin > amikacin > gentamicin. The results from the tetracyclines are consistent with the expectation that these compounds would not be nephrotoxic in vitro since in vivo investigations suggest hormonal mediation is required, and would be hepatotoxic in vitro because of direct action of these xenobiotics on liver cells in vivo. Similarly, the aminoglycosides were more toxic to the proximal kidney cells than to the distal cells as seen in vivo. These results suggest that continuous cell lines may provide important information in the assessment of xenobiotic cytotoxicity.