Induction of thioguanine-resistant mutations in human uroepithelial cells by 4-aminobiphenyl and its N-hydroxy derivatives.

The mutagenic potentials of the human bladder carcinogen 4-amino-biphenyl (ABP) and three of its proximate carcinogenic metabolites, N-hydroxy-4-aminobiphenyl (N-OH-ABP), N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and N-acetoxy-4-acetylaminobiphenyl (N-OAc-AABP) were tested on a prime human target cell type for carcinogenesis, human uroepithelial cells (HUC). SV-HUC (PC), a near diploid, clonally derived, nontumorigenic SV40-immortalized human uroepithelial cell line that is transformable to tumorigenicity after exposure to ABP and its metabolites, was used for quantitative mutation assays. The end point used was the induction of mutations in the hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus, selected using 6-thioguanine resistance (TGr). A single, 24-h exposure of SV-HUC to ABP, N-OH-ABP, N-OH-AABP, or N-OAc-AABP caused a statistically significant, dose-dependent increase in mutation frequency resulting in a 2-30-fold increase in the number of TGr mutants in carcinogen-exposed groups compared to untreated controls. These chemicals were similarly mutagenic towards MC-T11, an SV-HUC-derived low grade tumor cell line that was also shown to be responsive to transformation (in a separate study) by ABP, N-OH-ABP, or N-OH-AABP as judged by the generation of higher grade tumors. In contrast, the mutagenic potencies of ABP and N-OH-ABP were lower when tested on a subclone of SV-HUC (BC) that is refractory to transformation by these chemicals. Thus, these data support a model of transformation in which ABP as well as its metabolites contribute to tumorigenic transformation and neoplastic progression of HUC by inducing mutations in susceptible target cell genes.     

Longitudinal relationships between lexical and grammatical development in typical and late-talking children.

PURPOSE: This study examined the longitudinal relationships between lexical and grammatical development in typically developing (TD) and late-talking children for the purposes of testing the single-mechanism account of language acquisition and comparing the developmental trajectories of lexical and grammatical development in late-talking and TD children. METHOD: Participants included 30 children identified as late talkers (LTs) at 2;0 (years;months), and 30 TD children matched on age, nonverbal cognition, socioeconomic status, and gender. Data were collected at 5 points between 2;0 and 5;6. RESULTS: Cross-lagged correlational analyses indicated that TD children showed evidence of bidirectional bootstrapping between lexical and grammatical development between 2;0 and 3;6. Compared with the TD group, LTs exhibited less evidence of syntactic bootstrapping. Linear mixed-effects modeling of language sample data suggested that the relationship between lexical and grammatical growth was similar for the 2 groups. CONCLUSION: Lexical and grammatical development were strongly related in both groups, consistent with the single-mechanism account of language acquisition. The results were mixed in terms of finding longitudinal differences in lexical-grammatical relationships between the TD and late-talking children; however, several analyses suggested that for late-talking children, syntactic growth may be less facilitative of lexical development.