Flow cytometric detection of tandem repeat mutations induced by various chemical classes.

To facilitate detection of genotoxicity from environmental mutagen exposure, we generated an in vitro enhanced green fluorescence protein (EGFP) reactivation assay that quickly and effectively detects frameshift mutations in tandem repeat sequences (TRS). Two murine cell lines, C3H10T1/2 and mismatch repair deficient MC2a, were stably transfected with EGFP reporter plasmids in which the EGFP constructs contain TRS that put the EGFP sequence out of frame. These included several 2, 3, 4, 5 and 6 bp repeat sequences, a control non-repetitive sequence and a human gene sequence containing a 4 bp repeat motif.

Testicular toxicity of candidate fuel additive 1,6-dimethoxyhexane: comparison with several similar aliphatic ethers.

Previous studies of the toxicity of candidate fuel additives identified severe testicular toxicity in animals exposed to 1,6-dimethoxyhexane (DMH). A series of studies were conducted to characterize the effects of DMH on spermatogenesis and to compare the effects of DMH with responses to structural similar aliphatic ethers. In the first study, sexually mature male rats were administered a single dose (600 mg/kg) of DMH, and subsets of animals were sampled at intervals post exposure (PE).

The influence of dietary isoflavone on the uterotrophic response in juvenile rats.

Current in vivo methods to identify and assess reproductive hazards of endocrine disrupting substances are often confounded by the presence of isoflavones (genistein, diadzein, glycitein), strongly hormonally-active substances, in the diet of laboratory rodents. However, studies that have attempted to study the influence of dietary isoflavone on qualitative and quantitative uterotrophic responses have been limited by the few doses of isoflavone tested, stress to the animals due to changing of the diet immediately prior to testing and/or comparing effects of diets of very different composition. The current study examined the effects of isoflavone on uterotrophic response by using immature female rats reared from conception on diets varying only in the amount of isoflavone concentrate (Novasoy) added to a virtually isoflavone-free soya-based diet.

Thyroid toxicity due to subchronic exposure to a complex mixture of 16 organochlorines, lead, and cadmium.

The human population in the industrialized world is ubiquitously exposed to complex mixtures of persistent pollutants that contaminate food, water, and air. A large number of these contaminants have been shown to cause significant toxicity to the hypothalamic-pituitary-thyroid (HPT) axis in laboratory animal studies, through a variety of mechanisms, although these effects occur at levels of exposure greatly in excess of common human exposure. While many of the mechanisms of thyroid toxicity of these substances are potentially complementary, little is known of the degree of interaction of common persistent contaminants on responses of the HPT axis.

Effects of subchronic exposure to a complex mixture of persistent contaminants in male rats: systemic, immune, and reproductive effects.

Human populations throughout the world are exposed daily to low levels of environmental contaminants. The consequences of potential interactions of these compounds to human endocrine, reproductive, and immune function remain unknown. The current study examines the effects of subchronic oral exposure to a complex mixture of ubiquitous persistent environmental contaminants that have been quantified in human reproductive tissues.