General subcellular effects of lead, mercury, cadmium, and arsenic.

Abstract

This working paper summarizes the known ultrastructural and biochemical effects of lead, mercury, cadmium, and arsenic on subcellular organeUle systems following in vivo administration. Documented metal-induced alterations in nuclear, mitochondrial, microsomal, and lysosomal functions are discussed in relation to their potential impact on cellular responses to other environmental agents. Each of the above elements has been found to interfere with normal cellular replication and genetic processes. Mitochondrial swelling and depression of respiratory function are discussed in relation to known metal-specific perturbations of mitochondrial heme biosynthetic pathway enzymes. Inhibition of microsomal enzyme activities and protein synthesis by lead and mercury is compared to the apparent absence of such effects following arsenic or cadmium exposure. Lysosomal uptake of all the metals is documented, but biochemical alterations in these structures have been reported for only mercury and cadmium. It is concluded that these toxic metals are capable of interacting with, and biochemicaly altering major cellular systems at dose levels below those required to produce signs of overt metal toxicity. The impact of these effects on cellular responses to other metals and xenobiotics in complex exposure situations is presently unknown, and further research is urgentiy needed in this area.

Arsenic exposure in a copper smelter as related to histological type of lung cancer

“…This view, consistent with most of the animal studies, regards arsenic as a cocarcinogen or cancer promoter rather than as a primary carcinogen [Fowler, 1978;Willenberg, 19781. Cancers resulting from the combined action of arsenic, plus different carcinogens or cocarcinogens, would, in this view, probably not have a consistent distribution of histologic types.…”

“…In further support of this possibility is the observation that arsenic interferes with DNA repair [Bencho, 1977;Fowler, 1978;Nordenson et al, 19781, and that it is a selenium antagonist, interfering with the possible anticarcinogenic action of selenium [Schrauzer, 19771. This view, consistent with most of the animal studies, regards arsenic as a cocarcinogen or cancer promoter rather than as a primary carcinogen [Fowler, 1978;Willenberg, 19781.…”

Further Studies on the Subcellular Distribution of Cd2+ in Cd-sensitive and Cd-resistant Strains of Saccharomyces cerevisiae

“…In contrast to the results with strain 301N, most of the cellular Cd2+ in the Cdsensitive strain lOlN was found in the pellet fraction (Fig. 2), indicating that many Cd2+-binding sites exist on the cell membrane or in the cell organelles (Solaiman et al, 1979;Fowler, 1978). Cell membranes and mitochondria contain many enzyme systems which are affected by Cd2+ (Nicholls et al, 1981 ;Vallee & Ulmer, 1972), resulting in the release of K+ from the cells (Nicholls et al, 1981 ;Stacey & Klaassen, 1981 ;Gadd & Mowll, 1983).…”

Subcellular Organelle Toxicity Caused by Arsenic Nanoparticles in Isolated Rat Hepatocytes

“…46 Since arsenicals have been reported to accumulate in lysosomes, it is possible that arsenic-induced lysosomal destabilization involves a Fenton-type and Haber-Weiss reaction. 47 These arsenic-induced reactions produce reactive hydroxyl radicals that cannot diffuse out of the lysosomes, resulting in further destabilizing of lysosomal membranes; hydrolytic enzymes are released and would eventually trigger the apoptosis. 48 Particle size reduction is believed to be the first and easiest way for increasing the drug dissolution rate.…”