Changes in muntjac fibroblasts associated with the acquisition of cadmium resistance. A pre-resistance, transitional and post-resistance study.
A series of cell lines with different levels of resistance to continuous cadmium exposure has been developed from an immortal but non-transformed muntjac fibroblast cell line. Concentrations accepted in their culture medium range from 0.1 microM for the cadmium sensitive parent line to 5 microM for the intermediate "cadmium-tolerant" line, to 5, 10, 20 and 50 microM for the four "cadmium-resistant" lines. The present paper follows the morphological changes which accompanied the development of resistance through a 20-month pre-resistance period, a relatively abrupt 6-week transitional period and a 3-year post-resistance period, during which time levels of cadmium resistance were increased. Initial changes which led to the cadmium-tolerant CR5 cell line included (i) increased efficiency in autophagocytosing damaged cell components and in ridding the cell of residual waste materials, (ii) a reduction in fluid filled vacuoles and (iii) improved recycling and/or replacement of cadmium-damaged cell membrane. With the advent of cadmium resistance the intracellular damage necessitating these activities disappeared, yet the series of changes which occurred included a massive build-up of Golgi and the appearance of a trans-Golgi tubular network in addition to cytoskeletal and membrane changes. Though metallothionein levels are greater in the cadmium-resistant variants, their increase appears inadequate on their own to account for the high levels of resistance. The post-resistance changes which accompanied each step-up in cadmium resistance included further membrane and glycocalyx changes, in addition to continued increases in Golgi bodies and tubular network. This paper details the morphological changes which occurred throughout the 5-year period, tests the direct dependence of each on the presence of cadmium and examines their possible contribution to a cadmium protective mechanism.
Ord
M J
MJ
Biology Department, Southampton University, UK.
Chibber
R
R
Bouffler
S D
SD
Courtney
T
T
D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D002460:Cell Line; D002462:Cell Membrane / Q000648:ultrastructure; D003260:Contact Inhibition / Q000187:drug effects; D003599:Cytoskeleton / Q000648:ultrastructure; D003670:Deer; D004351:Drug Resistance; D004721:Endoplasmic Reticulum / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D005978:Glutathione / Q000378:metabolism; D006056:Golgi Apparatus / Q000648:ultrastructure; D008668:Metallothionein / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D013997:Time Factors; D014741:Video Recording
D002104:Cadmium; D008668:Metallothionein; D005978:Glutathione