Molecular and somatic-cell genetic analysis of metal-resistance mechanisms in mammalian cells
Combined molecular genetic analyses and somatic cell systems were utilized to delineate factors involved in metal metabolism. Somatic cells derived by selection procedures using toxic heavy metals were used to define primary factors involved in acquisition of metal resistance. Such cell variants permitted isolation of the specific genes involved in conferring heavy metal binding proteins, the metallothioneins. (MT). These isolated genes provided the molecular probes to dissect the multiple levels of control and organization of this one set of genes responsible for metal resistance. Studies on the roles of MT in metal resistance used these variants and cell lines derived from human tumors to illustrate that MTs play an important but not exclusive role in cadmium detoxification. Studies on Cd/sup + +/ responses in human tumor derived cell lines showed several orders of magnitude differences in Cd/sup + +/ sensitivity in lines having similar MT responses. Analysis of cultured normal blood cell responses showed that the most Cd/sup + +/ resistant population, the granulocytes, did not produce significant quantities of MT. The results presented here further show a lack of correlation between MT and cytotoxic responses to Cd/sup + +/ in freshly cultured human leukemic peripheral blood cells. In these, enhanced Cd/sup + +/ uptake may be a factor determining enhanced sensitivity. Theses results together indicate that an adequate understanding of cellular responses to toxic metals will not be provided by elucidation of the role(s) of one or a few known metal binding proteins such as MT. Other factors and systems that modulate cellular uptake and sensitivity must first be defined.
- Research Organization:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- DOE Contract Number:
- W-7405-ENG-36
- OSTI ID:
- 5518883
- Report Number(s):
- LA-UR-83-2677; CONF-8309164-1; ON: DE84001322
- Resource Relation:
- Conference: Molecular and cellular approaches to understanding mechanisms of toxicity conference, Boston, MA, USA, 1 Sep 1983
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CADMIUM
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
DETOXIFICATION
METABOLISM
COPPER
METALLOTHIONEIN
BIOLOGICAL FUNCTIONS
ZINC
CADMIUM 109
CELL CULTURES
EXPERIMENTAL DATA
LEUKEMIA
MOLECULAR BIOLOGY
TRACER TECHNIQUES
BETA DECAY RADIOISOTOPES
CADMIUM ISOTOPES
DATA
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
EVEN-ODD NUCLEI
FUNCTIONS
HEMIC DISEASES
INFORMATION
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
METALLOPROTEINS
METALS
NEOPLASMS
NUCLEI
NUMERICAL DATA
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
TRANSITION ELEMENTS
YEARS LIVING RADIOISOTOPES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)