Review Article: Strain as a Determinant Factor in the Differential Responsiveness of Rats to Chemicals

Abstract

The beneficial effects derived from the use of chemicals in agriculture, energy production, transportation, pharmaceuticals, and other products that improve the quality of life are clearly established. However, continued exposure to these chemicals is only advantageous in conditions where the benefit far outweighs toxic manifestations. By law, determination of risk of toxicity necessitates the use of laboratory animals to establish whether chemical exposure is safe for humans. To simulate the human condition, it is incumbent upon investigators to choose a species in which pharmacokinetic and toxicokinetic principles are established and resemble those of humans. Some of the advantages to the use of rat in chemical toxicity testing include (a) similarities in metabolism, anatomy, and physiological parameters to humans; (b) the short life span, especially for carcinogenesis study; (c) the availability, ease of breeding, and maintenance at a relatively low cost; and (d) the existence of a large database to enable comparison of present to reported literature findings. However, the choice of rat can be complicated by several factors such as sex, age, and nutrition, but especially strain, where currently there are over 200 different strains of rat known to exist. The aim of this review is to demonstrate that there are differences in the responsiveness of rat strains to chemicals and that the susceptibility observed is dependent on the tissue examined. It is evident that the genotype differs among strains, and this may be responsible for differences in sensitivities to chemicals. Awareness of strain as a factor in susceptibility to toxicant action needs to be taken into account in interpretation of relevance of risk of toxicity for humans.

Evaluation of Novel Biomarkers of Nephrotoxicity in Two Strains of Rat Treated with Cisplatin

“…Han-Wistar rats exhibited greater sensitivity to nephrotoxic injury due to cisplatin than the Sprague-Dawley rats, as indicated by the occurrence of changes at earlier time points and at lower dosages in the Han-Wistar rats. Strain differences in the severity of toxic response to chemicals, including nephrotoxicants, are known to occur (Kacew, Ruben, and McConnell 1995;Mazze, Cousins, and Kosek 1973;Newton et al 1983aNewton et al , 1983bTarloff, Goldstein, and Hook 1989). However, this would not be a confounding factor in the evaluation of the diagnostic utility of the biomarkers in this study since biomarkers were assessed at the individual animal level relative to time-matched control animals of the same strain.…”

Comparative and Correlative Neuroanatomy for the Toxicologic Pathologist

“…Many neurobiologic differences have been reported that could impact the choice of 1 species over another for neurotoxicity bioassays (11,20,24,53,85). Examples include disparities in neurochemistry, behavior, and xenobiotic responsiveness that exist between rats of different strains, sexes, and ages (52,70,78) and between rats and mice (103). Subtle differences also exist among various primate species (98).…”

“…In like manner, the degree of surface partitioning varies markedly among species in direct relation to phylogenetic position. Therefore (25) and monkey (131) (30,122) and rat (77,78) (36,119,144,161,169). Biochemical disparities, such as regional differences in the quantities and circadian cycling of neurotransmitters (110) and hormones (164), have been documented in rodents (24) and primates (169).…”

“…Neuroanatomic comparisons among normal animals in phylogenetically distant species may be quite complicated. Interspecies extrapolation is especially difficult if xenobiotic-induced neural responses differ among animals of different strains, genders, and ages (14,24,39,43,77,78,155). These challenges combine to make the neuropathology examination a daunting event, even for the seasoned practitioner.…”

Rodent Models of Cardiopulmonary Disease: Their Potential Applicability in Studies of Air Pollutant Susceptibility

“…The potential for preexistent disease to animals and considered in estimations of alter adverse responses to toxicant exposure human health risk (1)(2)(3)(4). A solid database is widely acknowledged but poorly under-on human susceptibilities related to prestood.…”