D. Warshawsky et al., CARCINOGENICITY OF 7H-DIBENZO [C,G]CARBAZOLE, DIBENZ[A,J]ACRIDINE ANDBENZO[A]PYRENE IN MOUSE SKIN AND LIVER FOLLOWING TOPICAL APPLICATION, Toxicology, 93(2-3), 1994, pp. 135-149
N-Heterocyclic aromatics are by-products of incomplete combustion of o
rganic material. The overall objective of this study was to determine
the relative carcinogenic potencies of 7H-dibenzo[c,g]carbazole (DBC)
and dibenz[a,j]acridine (DBA) in a bioassay of complete carcinogenicit
y on mouse skin in a sensitive strain (Hsd:ICR(Br)) which has been use
d in metabolism and DNA binding studies of N-heterocyclic aromatics. N
o-treatment, acetone and benzo[a]pyrene (BaP)-treated animals were use
d as negative and positive control groups. DBC (50 nmol), DBA (50 nmol
), BaP (50 nmol) or DBC plus BaP (25 nmol + 25 nmol) were applied twic
e weekly in 50 mu l acetone to the backs of 50 female mice/group for 9
9 weeks or until the appearance of a tumor. DBC, DBA, BaP and DBC plus
BaP produced skin tumors in 43, 32, 49 and 42 of 50 mice each based o
n weekly visual observations with latent periods of 55.1, 62.2, 33.4 a
nd 33.8 weeks, respectively. The histopathology data indicated primary
skin lesions in 42, 27, 48 and 47 mice for DBC, DBA, BaP and DBC plus
BaP, respectively. In addition, primary liver lesions in 37 mice were
present in the DBC group. The morphological and morphometric data ind
icated a significant increase (P less than or equal to 0.05) in mononu
clear cells in the dermis for the BaP and DBC plus BaP groups relative
to the control group. Significant increases' (P less than or equal to
0.05) were observed in the nuclear area, nucleoli per nucleus and cel
lular area of hepatocytes in the DBC treatment group relative to the c
ontrol group. These data indicate that DBC is a potent liver carcinoge
n as well as a skin carcinogen following topical application.